Cure obesity? It is possible, but difficult...

Obesity is a disease that can be curedA.M.Mkrtumyan, MD, Professor, E.V.Biryukova, PhD, Associate Professor, R.I.Stryuk, MD, Professor, P.L.Bindita, MGMSU, Moscow

Journal "Medical Council" No. 2-2007

Obesity is a serious problem of modern society. By the beginning of the XXI century, 20-25% of the adult population of the planet were obese, and about 50% were overweight. The urgency of the problem lies in the fact that everywhere there is a rapid increase in the number of obese people, including children and adolescents. According to epidemiological forecasts, 40% of men and 50% of women will be obese by 2025. The economic costs of treating obesity and its complications are very high – in the developed countries of the world they account for 8-10% of all healthcare costs.

Overweight in childhood is a significant predictor of obesity in the future: 50% of children who were overweight at the age of 6, becoming adults, are obese. For overweight teenagers, this probability increases to 80%.

Unfortunately, not only patients, but also some doctors do not consider obesity a serious disease and often underestimate its negative impact on health, especially on the cardiovascular system. When treating diseases causally associated with obesity, doctors do not always insist on reducing body weight, despite the fact that this measure reduces the clinical manifestations of these diseases and increases the effectiveness of therapy. So, for every 1.0 kg of body weight loss, the concentration of total cholesterol decreases by 0.05 mmol/l, LDL cholesterol – by 0.02 mmol /l, triglycerides – by 0.015 mmol /l, and the level of HDL cholesterol increases by 0.009 mmol /L. In addition, a decrease in body weight by 5-6 kg reduces by 58% the risk of further progression of carbohydrate metabolism disorders – the development of type 2 diabetes mellitus in patients with impaired glucose tolerance (HTG).

Often obese patients practice self-medication, which worsens the course of the disease and reduces the effectiveness of therapy. At the same time, practice shows that more than 90% of people who have lost body weight gain their weight again within a year, and in some cases the body weight becomes even greater than the original one.

The development of this disease largely depends on genetic factors. However, such typical features of a modern lifestyle as overeating, high-calorie nutrition, the predominance of fats in the diet, low and irregular physical activity, bad habits, as well as a number of social and behavioral factors are no less important for the development of obesity than genetic predisposition.

It is known that obesity significantly reduces a person's life expectancy and increases the likelihood of developing a number of serious diseases. Thus, obese patients have a 50% higher risk of death than those with normal body weight. About 8 million Americans suffer from pathological obesity, which ranks second among the causes of so-called preventable mortality, which claims about 400,000 lives annually. In addition, more than 40% of obese patients die from chronic heart failure.

With the widespread prevalence of obesity, the number of diseases and conditions caused by it is also growing. Thus, 2/3 of obese patients develop DM2 and, on the other hand, about 90% of DM2 patients are overweight.

As mentioned earlier, there is a direct relationship between obesity and cardiovascular diseases. The prevalence of arterial hypertension (AH) among obese men and women is 41.9 and 37.8%, respectively. Over the age of 18, a 1.0 kg increase in body weight increases the risk of hypertension by 5%, and an increase of 8.0-10.9 kg increases the risk of developing cardiovascular diseases by 1.6 times. Middle-aged people with overweight are 50% more likely to develop hypertension than people with normal weight. Obesity contributes to the increase in hypertension, increases the risk of early vascular complications, and also directly causes a violation of myocardial contractility and accelerates the development of left ventricular hypertrophy, which is currently considered as an important factor in the increased risk of sudden death. A decrease in body weight in the range of 5.0-9.9 kg reduces the risk of hypertension by 15%.

With obesity, atherogenic disorders of the blood lipid spectrum increase with the rapid development and progression of vascular atherosclerosis. Disorders of lipoprotein metabolism are a well–known risk factor for the development of diseases of the cardiovascular system. Pathomorphological studies have shown that primary atherosclerotic changes appear even in young obese patients. Thus, 12% of adolescents had atherosclerotic changes in the right coronary artery, and 50% of children aged 2-15 years had fat strips in the coronary arteries. Along with hypercholesterolemia, an increase in the concentration of TG and a decrease in the concentration of HDL cholesterol are especially characteristic.

Obese patients also have an increased risk of various oncological diseases – colon cancer, endometrial cancer, prostate cancer, gallbladder, esophageal adenocarcinoma, etc.

Obesity is often combined with obstructive sleep apnea syndrome (OSA), which significantly reduces life expectancy and can cause sudden death. The prevalence of OSA among obese patients is 38-55%, which is significantly higher than in the general population.

Obesity is regarded as a factor contributing to the progression of chronic kidney diseases. In such patients, the survival rate of a kidney transplant is noticeably reduced, and in persons with a BMI > 30 kg /m2 who underwent unilateral nephrectomy, proteinuria appears very soon, and kidney function steadily worsens.

Obesity is also a risk factor for the development of deep vein thrombosis and thromboembolism, especially in the presence of other predisposing factors (fracture of the proximal femur, major surgical operations, prolonged air travel).

The vast majority of patients with chronic calculous cholecystitis and non-alcoholic fatty hepatosis are obese. In addition, patients suffering from chronic viral hepatitis C and obesity are significantly less amenable to interferon therapy.

We have to admit that there are many doctors who are overweight or obese. However, many of them do not seek treatment or have failed in the fight against excess weight and are often skeptical of the recommendations about the need to reduce body weight. As a result, patients lose motivation for non-pharmacological methods of treating obesity and concomitant diseases, as well as generally lose confidence in the doctor's recommendations.

In clinical practice, it is always necessary to take into account that with systematic use, some medications contribute to an increase in body weight:

• antipsychotic drugs (olanzepine, closepine, respiridon);
• tricyclic antidepressants;
• lithium preparations;
• anticonvulsants (valproate, carbamazepine);
•  α-, β-blockers;
• hypoglycemic drugs: sulfonylurea derivatives, thiazolidinediones;
• cc;
• hormonal contraceptives;
• antihistamines, etc.

One of the most informative indicators for assessing weight and the degree of obesity is BMI, determined by dividing the body mass index in kilograms by the growth index expressed in meters and squared (kg/m2) (Table).

Of great clinical importance is not only the severity of obesity, but also the nature of the distribution of subcutaneous fat. Obesity is regarded as visceral-abdominal if the ratio of waist circumference to hip circumference is more than 0.9 in men and 0.85 in women. With this type of obesity, serious hormonal and metabolic disorders are observed already at a young age, even with relatively low BMI values, and the risk of developing related diseases increases dramatically.

Obesity therapy is quite a difficult task, since it is a chronic disease that requires long–term, systematic observation and treatment. Modern approaches to the treatment of the disease are based on the use of non-pharmacological methods of treatment, which, if necessary, are supplemented with pharmaceuticals.

The main goal of the treatment of obesity, along with weight loss, is to prevent the development of concomitant diseases, primarily cardiovascular, or to improve their course, improving the quality of life of the patient. To improve the health of obese patients, it is not necessary to strive to achieve an ideal body weight. According to modern recommendations, a clinically significant decrease in body weight is 5% of the initial value, after achieving this, it is necessary to take measures to maintain the achieved results for a long time and prevent relapses of the disease.

Unfortunately, in practice, non-pharmacological methods of obesity therapy are not fully used by doctors. Practical recommendations for lifestyle modification should include an individual calculation of the diet, changing the stereotype of nutrition, giving up bad habits, increasing physical or household loads.

The basis of obesity therapy is a low-calorie diet and fat restriction. A decrease in body weight and a negative energy balance are achieved by reducing the physiological caloric content of the diet by 500-600 kcal / day, while the daily caloric content should not be less than 1200 kcal for women and 1500 kcal for men. The diet should contain carbohydrates (slow–digesting) – 55-60%, proteins – 15%, and fat no more than 25-30% of the daily diet, including saturated fats – less than 7-10%, polyunsaturated – up to 10%, monounsaturated - less than 20%, cholesterol less than 300-200 mg. The fiber content should be more than 20-25 g / day. Moderate salt intake is recommended (up to 5 g per day). To monitor the effectiveness of treatment, the patient should keep a food diary, where they should daily enter information about all meals: a complete list of products and their volume, the amount of liquid consumed.

At the present stage, the so–called "fashionable diets" have become widespread, some with a restriction of fats, others with a restriction of carbohydrates, etc. The general provisions regarding the role of diet can be formulated as follows:

• Any restrictions in the diet lead to a decrease in body weight.
• Reducing the caloric content of the daily diet is the main determinant of weight loss.
• Weight loss is less dependent on the ratio of macronutrients in the diet.
• The degree of weight loss is the main predictor of compensation for metabolic disorders.

Benefits of a fat-restricted diet

• Fat content < 20% of the total diet.
• High content of carbohydrates (fiber).
• Restriction of animal proteins.
• Reduction of body weight due to the mass of fat.
• There is no feeling of hunger due to a large amount of food.
• Reduction of blood pressure, glucose, leptin, TG, OHL, LDL.

Disadvantages of a fat-restricted diet

• Reduction of HDL
• The need for additional intake of multivitamins and trace elements (B12, E, iron, zinc, phosphorus, calcium)
• Flatulence

It is important to note that weight loss is always more significant against the background of diet therapy, combined with increased physical activity, which reduces the addiction to eating food, especially rich in fats. In 1998, WHO experts proposed recommendations on diet therapy for obesity:

1. Hypocaloric nutrition at the stage of weight loss.
   • At least 1200-1500 kcal per day.
2. Eucaloric nutrition at the stage of stabilization of body weight.
   • Calculation according to the WHO formula, 1998:
     • For women 18-30 years old (0.06 x weight in kg + 2) x 240.
     • For women 31-60 years old (0.03 x weight in kg + 3.5) x 240.
     • For men 18-30 years old (0.06 x weight in kg + 3) x 240.
     • For men 31-60 years old (0.05 x weight in kg + 3.7) x 240.
3. Balanced by macronutrients.
   • Proteins – 15%, fats - 25%, carbohydrates - 60%.
4. Regular.
   • 3 main meals and 2 snacks.
5. Diverse.
   • Taking into account tastes, material possibilities, traditions.

Patients are recommended regular physical activity (dosed walking, swimming, exercise bike) of moderate intensity (4-5 classes per week for 30-45 minutes), because at the beginning of therapy, patients are often unable to perform prolonged and intensive exercises. Unfortunately, despite the proven effectiveness of combining diet therapy with increased physical activity, only 20% of patients seeking to reduce body weight use these therapeutic approaches simultaneously.

A short-term reduction in body weight is easy to achieve with the help of diet and physical activity, but most people fail to maintain the result for a long time. Among patients who have lost weight through diet and exercise, about 2/3 gain weight again within a year, and most of them continue to gain weight in the next 5 years of life (2). In cases where diet and physical activity do not provide the desired weight loss and / or do not allow for a long time to maintain weight at the achieved level, as a supplement, the pharmacotherapy of obesity is used, which does not eliminate the need for non-drug treatment methods. It is indicated in patients with a BMI ≥ 30 kg / m2, and in the visceral form of obesity with a BMI ≥ 27 kg / m2.

Unfortunately, currently the possibilities of pharmacotherapy of obesity are very limited, because there are not so many drugs that can not only reduce body weight, but also prevent the development and progression of diseases associated with obesity.

The following drugs are used in the pharmacotherapy of obesity.

Sibutramine (miridia) is a selective serotonin and norepinephrine reuptake inhibitor in CNS synapses. It contributes to the normalization of eating behavior, as it enhances and prolongs the feeling of satiety, which causes a decrease in energy intake by reducing the amount of food consumed, and also increases energy consumption, stimulating thermogenesis. An important mechanism of action of the drug is an increase in the metabolic rate, which occurs in the process of weight loss. This helps to maintain the achieved body weight during therapy. In addition to reducing body weight, positive dynamics is achieved from the indicators of lipid and carbohydrate metabolism.

According to the recommendations, sibutramine is taken 10 mg 1 time a day before breakfast. If after 4 weeks the weight loss was less than 2 kg, then the daily dose is increased to 15 mg. Therapy should be discontinued if, after 12 weeks of treatment, it was not possible to achieve a 5% reduction in body weight.

The most significant side effects of the drug are hypertension and an increase in heart rate. Other undesirable effects include dry mouth, headache, insomnia, constipation, decreased effectiveness of hypotensive therapy. The drug is contraindicated in refractory hypertension, severe coronary heart disease, circulatory insufficiency, as well as in renal and hepatic insufficiency, epilepsy, angle-closure glaucoma.

Orlistat (xenical) is a peripheral drug that does not have systemic effects. The pharmacological effect of the drug is due to its ability to inactivate gastrointestinal lipase, which prevents the breakdown and subsequent absorption of about 30% of fats. As a result, there is a chronic lack of energy, which contributes to weight loss. Orlistat is prescribed 120 mg 3 times a day during or within an hour after meals, subject to the presence of fats in the food. In combination with a moderately hypocaloric diet, the drug significantly reduces body weight, prevents repeated weight gain, improves the course of concomitant diseases and improves the quality of life. Orlistat is recommended for long-term weight control in obese patients. Contraindications to the appointment are: malabsorption syndrome, hypersensitivity to the drug or its components.

Of great interest from the point of view of possible use for the treatment of obesity, especially in the presence of carbohydrate metabolism disorders, is metformin, which increases hepatic and peripheral sensitivity to endogenous insulin without acting on its secretion. The drug slows down the absorption of carbohydrates in the gastrointestinal tract, and also reduces appetite. In this regard, metformin therapy is accompanied by a decrease or stabilization of body weight, as well as a decrease in the deposition of visceral fat.

It is important to note that metformin has a cardiovascular protective effect associated with the hypolipidemic and antiatherogenic effect of the drug, its beneficial effect on lipid metabolism (reduces the oxidation of free fatty acids by 10-30%), endothelial function, vascular reactivity, hemostasis system and blood rheology, in particular by reducing hypercoagulation and platelet hyperactivity.

Treatment with the drug begins with a dose of 500-850 mg, taken during dinner or at night. In the future, the daily dose of the drug increases by 500-850 mg every 1-2 weeks. The maximum recommended dose for obese patients is 1500-1700 mg / day. in the mode of 2-3 receptions.

Adequate behavioral therapy aimed at motivating the patient to lose weight, increase physical activity and constant implementation of measures to combat obesity is essential in the treatment of obesity, which is the key to successful therapy and prevention of relapses of the disease.

Surgical treatment of obesity is used with a BMI of ≥ 40 kg / m2 (in case of ineffectiveness of pharmacotherapy), as well as in patients with a BMI of 35 kg / m2 or more, if there is a serious concomitant pathology (hypertension, coronary heart disease, circulatory insufficiency, DM 2, OSA).

The effectiveness of antihypertensive pharmacotherapy in this category of patients is significantly lower compared to patients with normal body weight, therefore normalization of blood pressure is achieved by a combination of several drugs and the use of large daily doses.

Thus, obesity is a widespread chronic disease with serious medical consequences. Pharmacotherapy of obesity should be considered as a supplement to non-drug methods of treatment of this disease based on lifestyle changes. Treatment of obesity is a complex, not fully developed problem, and its solution will not only improve the quality and increase the life expectancy of patients, but also significantly reduce morbidity and mortality from complications of obesity.

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03.06.2008