Metabolic syndrome: diagnosis, treatment, obesity in MS in women and men. Metabolic syndrome in women: causes and treatment

Metabolic syndrome is a complex of metabolic disorders that indicates that a person has an increased risk of cardiovascular disease and type 2 diabetes. The reason for this is the poor sensitivity of tissues to the action of insulin. Treatment of metabolic syndrome is... And there is another useful drug, which you will learn about below.

Insulin is the “key” that opens the “doors” on the cell membrane, and through them glucose penetrates from the blood. With metabolic syndrome, the patient's blood sugar (glucose) and insulin levels increase. However, not enough glucose enters the cells because the “lock rusts” and insulin loses its ability to open it.

This metabolic disorder is called, i.e., excessive resistance of body tissues to the action of insulin. It usually develops gradually and leads to symptoms that are used to diagnose metabolic syndrome. It is good if the diagnosis can be made in time so that treatment can prevent diabetes and cardiovascular diseases.

Many international medical organizations are developing criteria by which metabolic syndrome can be diagnosed in patients. In 2009, the document “Agreeing on the definition of metabolic syndrome” was published, which was signed by:

• US National Heart, Lung, and Blood Institute;
• World Health Organization;
• International Society of Atherosclerosis;
• International Association for the Study of Obesity.

According to this document, metabolic syndrome is diagnosed if the patient has at least three of the criteria listed below:

• Increase in waist circumference (in men >= 94 cm, in women >= 80 cm);
• Blood triglyceride levels exceed 1.7 mmol/L, or the patient is already receiving medications to treat dyslipidemia;
• High-density lipoproteins (HDL, “good” cholesterol) in the blood - less than 1.0 mmol/l in men and below 1.3 mmol/l in women;
• Systolic (upper) blood pressure exceeds 130 mmHg. Art. or diastolic (bottom) blood pressure exceeds 85 mm Hg. Art., or the patient is already taking medications for hypertension;
• Fasting blood glucose level >= 5.6 mmol/L, or therapy to lower blood sugar.

Before the advent of new diagnostic criteria for metabolic syndrome, obesity was a prerequisite for diagnosis. Now it has become just one of five criteria. Diabetes mellitus and coronary heart disease are not components of metabolic syndrome, but independent serious diseases.

Treatment: responsibility of the doctor and the patient himself

Treatment goals for metabolic syndrome:

• reducing body weight to a normal level, or at least stopping the progression of obesity;
• normalization of blood pressure, cholesterol profile, triglyceride levels in the blood, i.e. correction of cardiovascular risk factors.

For real It is currently impossible to cure metabolic syndrome. But you can control it well, to live a long healthy life without diabetes, heart attack, stroke, etc. If a person has this problem, then its therapy must be carried out for life. An important component of treatment is educating the patient and motivating him to switch to a healthy lifestyle.

The main treatment for metabolic syndrome is diet. Practice has shown that it is useless to even try to adhere to any of the “hunger” diets. You will inevitably fall off sooner or later, and the excess weight will immediately return. We recommend that you use it to control metabolic syndrome.

Additional measures for the treatment of metabolic syndrome:

• increased physical activity improves tissue sensitivity to insulin;
• quitting smoking and excessive alcohol consumption;
• regularly measuring blood pressure and treating hypertension if it occurs;
• control of “good” and “bad” cholesterol, triglycerides and blood glucose.

We also advise you to inquire about a medicine called. It has been used since the late 1990s to increase the sensitivity of cells to insulin. This drug is of great benefit to obese and diabetic patients. And to date, he has not been shown to have any side effects more severe than occasional cases of stomach upset.

Most people diagnosed with metabolic syndrome benefit greatly from limiting carbohydrates in their diet. When a person switches to a low-carbohydrate diet, they can expect:

• the level of triglycerides and cholesterol in the blood is normalized;
• blood pressure will decrease;
• he will lose weight.

Get recipes for a low-carb diet

But if a low-carbohydrate diet and increased physical activity do not work well enough, then together with your doctor you can add metformin (Siofor, Glucophage) to them. In the most severe cases, when the patient has a body mass index > 40 kg/m2, surgical treatment of obesity is also used. It's called bariatric surgery.

How to normalize cholesterol and triglycerides in the blood

With metabolic syndrome, patients usually have poor results on blood tests for cholesterol and triglycerides. There is little “good” cholesterol in the blood, and “bad” cholesterol, on the contrary, is elevated. Triglyceride levels are also elevated. All this means that the vessels are affected by atherosclerosis, a heart attack or stroke is not far off. Blood tests for cholesterol and triglycerides are collectively called a lipid profile. Doctors love to talk and write, they say, I’m sending you to get tested for your lipid spectrum. Or worse - the lipid spectrum is unfavorable. Now you will know what it is.

To improve blood test results for cholesterol and triglycerides, doctors usually prescribe a low-calorie diet and/or statin medications. At the same time, they pretend to be smart, trying to look impressive and convincing. However, a starvation diet does not help at all, and pills help, but cause significant side effects. Yes, statins improve cholesterol blood test results. But whether they reduce mortality is not yet a fact... there are different opinions... However, the problem of cholesterol and triglycerides can be solved without harmful and expensive pills. Moreover, it may turn out to be easier than you think.

A low-calorie diet usually does not normalize cholesterol and triglycerides in the blood. Moreover, in some patients, test results even worsen. This happens because a low-fat “starvation” diet is overloaded with carbohydrates. Insulin converts the carbohydrates you eat into triglycerides. But it’s precisely these same triglycerides that I would like to have less in my blood. Your body cannot tolerate carbohydrates, which is why metabolic syndrome has developed. If you do not take action, it will smoothly turn into type 2 diabetes or suddenly end in a cardiovascular catastrophe.

They won't beat around the bush for long. Perfectly solves the problem of triglycerides and cholesterol. The level of triglycerides in the blood normalizes after 3-4 days of following it! Get tested and see for yourself. Cholesterol improves later, after 4-6 weeks. Get your blood tested for cholesterol and triglycerides before starting your “new life,” and then again. See if a low-carb diet actually helps! At the same time, it normalizes blood pressure. This is the real prevention of heart attack and stroke, and without the painful feeling of hunger. Blood pressure and heart supplements are a good addition to your diet. They cost money, but the expense is worth it because you will feel much more alert.

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1. Task 1 of 8

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   What is a sign of metabolic syndrome:

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   Of all the above, only hypertension is a sign of metabolic syndrome. If a person has fatty liver disease, then he probably has metabolic syndrome or type 2 diabetes. However, fatty liver is not officially considered a sign of MS.

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   How is metabolic syndrome diagnosed using cholesterol tests?

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   The official criterion for diagnosing metabolic syndrome is only reduced “good” cholesterol.

3. Task 3 of 8

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   What blood tests should be taken to assess the risk of a heart attack?

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4. Task 4 of 8

   4 .

   What normalizes triglyceride levels in the blood?

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   The main remedy is a low-carbohydrate diet. Physical exercise does not help normalize blood triglyceride levels, except in professional athletes who train 4-6 hours a day.

5. Task 5 of 8

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   What are the side effects of statin cholesterol medications?

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Description:

Metabolic syndrome (MS, syndrome X, insulin resistance syndrome) is a set of metabolic disorders, including excess body weight with abdominal type formation, insulin resistance, dyslipidemia and/or. Other symptoms of MS are also observed: microalbuminuria, disorders of the hemostatic system.
The frequency of MS varies somewhat depending on the inclusion criteria. However, the dependence on age is clearly established. In the USA, MS was diagnosed in 6.7% of those examined at the age of 20-29 years, in 43.6% - 60-69 years, and in 42% - 70 years and older. According to a WHO study, in the population of Novosibirsk aged 25-64 years, the frequency of MS was 40%.

Causes:

Etiology unknown. There are studies that indicate the role of the following factors in the development of MS:
■ increasing the tone of the sympathetic nervous system;
■ insulin resistance;
■ hyperandrogenism;
■ deficiency of insulin-like growth factor;
■ the role of pro-inflammatory cytokines (TNF-a, C-reactive protein, IL-6, IL-10).
Metabolic syndrome is a prestage of type 2 diabetes mellitus; it differs from the latter in stable diabetes mellitus, since insulin resistance at this stage is suppressed due to hyperinsulinemia. Reducing body weight by increasing physical activity and an adequate regimen reduces the risk of developing type 2 diabetes by 30-50% already at this stage.
The influence of sex hormones on lipid tissue:
Estrogens:
- increased lipoprotein lipase activity in the femoral-gluteal region;
- accumulation of lipids to provide energy reserves during pregnancy and lactation.
Progesterone:
- progesterone receptors are found in the abdominal subcutaneous fat;
- participates in the regulation of adipose tissue metabolism;
- is a competitor of glucocorticoids for their receptors in fat cells in the late luteal phase, increases energy expenditure;
- in postmenopause, the lack of progesterone explains the slowdown in metabolism.
Regulation of leptin production by adipocytes by estrogen occurs through a positive feedback mechanism. Leptin is a protein hormone synthesized by fat cells that signals the brain about the threshold of saturation, about the sufficiency of energy in the body.
The nature of the distribution of adipose tissue is determined by sex hormones: estrogens and progesterone are responsible for the localization of fat in the gluteal-femoral region (gynoid), androgens - in the abdominal region (android).
Adipose tissue is the site of extragonadal synthesis and metabolism of estrogens, in which P450 aromatase takes part.
Abdominal and especially visceral obesity is a risk factor for cardiovascular diseases, which is due to the specific anatomical and morphophysiological properties of such adipose tissue. Its blood supply improves, metabolic processes intensify, and fat cells have a high density of β-adrenergic receptors (their stimulation leads to lipolysis) with a relatively low density of α-adrenergic receptors and insulin receptors, the stimulation of which blocks lipolysis.  
Intense lipolysis in the adipose tissue of the abdominal-visceral region leads to an increase in the level of free fatty acids in the systemic circulation, which causes metabolic disorders characteristic of abdominal obesity: insulin resistance, increased levels of glucose, insulin, VLDL and triglycerides in the blood.
In insulin resistance, lipid oxidation is not suppressed and, accordingly, large amounts of free fatty acids are released from fat cells. In addition, excess free fatty acids activate gluconeogenesis, accelerate the synthesis and impair the elimination of VLDL-C and triglycerides, which is accompanied by a decrease in HDL-C levels. Dyslipoproteinemia, in turn, aggravates the state of insulin resistance, as evidenced, for example, by a decrease in the number of insulin receptors in target tissues with an increase in LDL-C levels.
The relationship between arterial hypertension and hyperinsulinemia is explained by:
■ increased reabsorption of sodium in the kidneys (antidiuretic effect);
■ stimulation of the sympathetic nervous system and the production of catecholamines;
■ increased proliferation of vascular smooth muscle cells and changes in the concentration of sodium ions in the vascular endothelium.
In menopausal MS, against the background of a deficiency of sex hormones, the concentration of sex steroid binding protein is reduced, which leads to an increase in the content of free androgens in the blood, which can themselves reduce the level of HDL and cause insulin resistance and hyperinsulinemia.
With obesity and insulin resistance, activation of pro-inflammatory reaction factors [TNFa, IL-6, plasminogen activator inhibitor-1 (PAI-1), free fatty acids, angiotensinogen II] occurs, which leads to endothelial dysfunction, oxidative stress, an inflammatory cascade of cytokines, promoting atherosclerotic changes and development of insulin resistance.
The relationship between the hemostatic system and insulin resistance is explained by the direct relationship between the level of insulin and the activity of factors VII, X and (IAP-1): insulin stimulates their secretion.
All components of metabolic syndrome: insulin resistance, dyslipoproteinemia, hyperactivity of the sympathetic nervous system are interrelated, but each of them is necessarily associated with abdominal obesity, which is considered a key sign of metabolic syndrome.

Symptoms:

The identification of MS is clinically significant due to the fact that this condition, on the one hand, undergoes reverse development, and on the other hand, is the basis of the pathogenesis of not only type 2, but also essential hypertension and.
In addition, according to the number of main risk factors for the development of coronary artery disease (upper type of obesity, impaired glucose tolerance, hypertension) included in MS, it is defined as a “deadly quartet”. MS includes the following main components:
■ insulin resistance;
■ hyperinsulinemia and increased levels of C-peptide;
■ impaired glucose tolerance;
■ hypertriglyceridemia;
■ decrease in HDL level and/or increase in LDL level;
■ abdominal (android, visceral) type of obesity;
■ AG;
■ hyperandrogenism in women;
■         increased content of glycated hemoglobin and fructosamine, the appearance of protein in the urine, impaired purine metabolism, .
MS can manifest itself in the form of any of the listed conditions; all components of the syndrome are not always observed.
Abdominal obesity is the main clinical symptom of metabolic syndrome.
Quite often the menstrual cycle is disrupted by type, metrorrhagia,. Polycystic ovaries are often detected.
Obesity increases the risk of:
-cardiovascular diseases;
- obstructive sleep apnea (snoring);
-diabetes mellitus;
-osteoarthritis;
- arterial hypertension;
- liver pathologies;
- rectal cancer;
-psychological problems;
-breast cancer.
Obstructive sleep apnea is observed in 60-70% of obese people. Characterized by daytime drowsiness, cardiac, myocardial ischemia, hyperventilation syndrome, pulmonary hypertension, cardiovascular failure,.

Treatment:

Goal of treatment: safe weight loss, restoration of reproductive functions if they are impaired.

Effective treatments for metabolic syndrome include:
A. formation and maintenance of the patient’s internal motivation to lose weight;
b. constant contact with the patient with setting and agreeing on intermediate treatment goals and monitoring their achievement.
Non-drug treatment:
- Lectures for patients.
- Rational hypo- and eucaloric nutrition.
- Increased physical activity.
- Normalization of lifestyle.
- Surgical treatment aimed at reducing the volume of the stomach.
Drug therapy:
- Selective serotonin and norepinephrine reuptake inhibitor (sibutramine) 10-15 mg per day: causes rapid onset and prolongation of a feeling of satiety and, as a result, a decrease in the amount of food consumed. The initial dose of sibutramine is 10 mg per day. If body weight loss is less than 2 kg over 4 weeks, the dose is increased to 15 mg per day. The drug is contraindicated in arterial hypertension.
- A peripherally acting drug, orlistat inhibits intestinal enzymatic systems, reducing the amount of free fatty acids and monoglycerides in the small intestine. The most effective dosage is 120 mg 3 times a day. Along with weight loss, during treatment with Xenical, normalization or a significant decrease in blood pressure, total cholesterol, LDL-C, and triglycerides was noted, which indicates a decrease in the risk of developing cardiovascular diseases. Xenical is well tolerated and safe.
- Antidepressants - selective serotonin reuptake inhibitors are indicated for patients with anxiety-depressive disorders, panic attacks and bulimia nervosa: fluoxetine - daily dose of 20 to 60 mg for 3 months or fluvoxamine 50-100 mg per day for 3 months.
Pathogenetic drug therapy for menopausal MS is hormone replacement therapy.

Losing body weight ultimately helps reduce the risk of developing cardiovascular diseases, prevent type 2 diabetes, and reduce the incidence of apnea and osteoarthritis. The mechanisms for achieving the final result after weight loss are quite complex and include:
- normalization of lipid metabolism;
- reduction in blood pressure, insulin concentrations, pro-inflammatory cytokines, risk of thrombosis, oxidative stress.
Since oligomenorrhea is often observed in women of reproductive age suffering from MS, as a rule, a decrease in body weight by 10% or more helps to normalize menstrual cycles in 70% of women and restore ovulation in 37% of women without hormonal drugs. HRT for MMS helps to reduce body weight, reduce the waist circumference/hip circumference index, normalize insulin levels and blood lipids.

Continued excess body weight increases the risk of cardiovascular diseases, damage to the musculoskeletal system, as well as some obstetric and gynecological diseases (endometrial hyperplasia, DUB, weakness of uterine contractility during childbirth).

Topic 9. Metabolic syndrome F-165

METABOLIC SYNDROME.

The concept of “syndrome” is usually interpreted as a set of symptoms, a symptom complex. When discussing the problem of metabolic syndrome, we mean not so much a set of symptoms as a combination of several diseases, united by the common initial links of pathogenesis and associated with certain metabolic disorders.

The evolution of ideas about the metabolic syndrome was formed throughout almost the entire twentieth century, and its beginning should be considered 1922, when in one of his works the outstanding Russian clinician G. F. Lang pointed out the close connection between arterial hypertension and obesity, lipid and carbohydrate disorders. metabolism and gout. The chronology of further events leading to the formation of the modern concept of metabolic syndrome can be briefly presented as follows:

30s XX century M. P. Konchalovsky combined excess body weight, gout, a tendency to diseases of the cardiovascular system and bronchial asthma with the term “arthritic constitution (diathesis)”;

1948 E. M. Tareev established the possibility of developing arterial hypertension against the background of excess body weight and hyperuricemia;

60s XX century J.P. Kamus designated the combination of diabetes mellitus, hypertriglyceridemia and gout with the term “metabolic trisyndrome”;

1988, the American scientist G. M. Riven proposed the term “metabolic syndrome X” to denote a combination of disorders of carbohydrate and lipid metabolism, including hyperinsulinemia (HI), impaired glucose tolerance (IGT), hypertriglyceridemia (HTG), decreased concentrations of high lipoprotein cholesterol density (HDL cholesterol) and arterial hypertension (AH).

Subsequently, other terms were proposed to nominate this complex of metabolic disorders: insulin resistance syndrome; plurimetabolic syndrome: dysmetabolic syndrome; the term “deadly quartet” was proposed by N. M. Kaplan to denote the combination of abdominal obesity (the most significant component of the syndrome, according to the author), IGT, arterial hypertension and GTG. Most authors attach insulin resistance to leading importance in the pathogenesis of these disorders, and from this point of view, the term “insulin resistance syndrome” proposed by S. M. Hafner seems the most appropriate. However, other researchers consider the role of abdominal obesity, rather than insulin resistance, to be more important and dominant in the development of this pathology.

The World Health Organization (WHO) (1999) recommended the use of the term “metabolic syndrome.” The International Diabetes Federation (2005) included the following disorders in the metabolic syndrome (MS):

abdominal obesity;

insulin resistance and compensatory hyperinsulinemia;

hyperglycemia (due to decreased glucose tolerance and/or high fasting glucose, up to the development of diabetes mellitus);

atherogenic dyslipidemia (a combination of high concentrations of triglycerides, small and dense particles of low-density lipoproteins (LDL) and low cholesterol concentrations);

arterial hypertension;

chronic subclinical inflammation (increased levels of C-reactive protein and other proinflammatory cytokines);

violation of the hemostasis system: hypercoagulation due to an increase in the concentration of fibrinogen and a decrease in the fibrinolytic activity of the blood - hypofibrinolysis.

Further research significantly expanded the list of MS components. In recent years, the symptoms, syndromes and diseases observed in metabolic syndrome have also begun to include:

liver steatosis;

obstructive sleep apnea;

early atherosclerosis;

hyperuricemia and gout;

microalbuminuria;

hyperandrogenism and polycystic ovary syndrome.

According to modern concepts, the dominant combinations in the clinical picture of MS are obesity, arterial hypertension, hypercholesterolemia and diabetes mellitus.

Thus, it seems possible to define metabolic syndrome as a complex of disorders of the neurohumoral regulation of carbohydrate, fat, protein and other types of metabolism, caused by insulin resistance and compensatory hyperinsulinemia and which is a risk factor for the development of obesity, atherosclerosis, type 2 diabetes mellitus, diseases of the cardiovascular system (hypertension , coronary heart disease) with subsequent complications, mainly of ischemic origin.

Etiology of metabolic syndrome

In the genesis of metabolic syndrome, a distinction is made between causes (internal factors) and factors in the development of metabolic disorders (external factors, risk factors). The causes of MS include: genetic condition or predisposition, hormonal disorders, disturbances in the processes of appetite regulation in the hypothalamus, disturbances in the production of adipocytokines by adipose tissue, age over 40 years. External factors of MS are physical inactivity, excess nutrition or violation of a diet adequate to the body's needs, and chronic stress.

The etiological effect of internal causes and external factors in the development of MS is characterized by complex relationships and the interdependence of the influence of their various combinations. The result of this action and at the same time the primary link in the pathogenesis of MS is insulin resistance (IR).

Mechanisms of formation of insulin resistance. Insulin resistance is understood as a violation of its biological action, manifested in a decrease in insulin-dependent glucose transport into cells and causing chronic hyperinsulinemia. IR, as a primary component of the pathogenesis of MS, is accompanied by impaired glucose utilization in insulin-sensitive tissues: skeletal muscles, liver, adipose tissue, and myocardium.

Genetic reasons leading to the development of insulin resistance and subsequent MS are caused by hereditarily fixed mutations in genes that control the synthesis of carbohydrate metabolism proteins. The metabolism of carbohydrates is ensured by a very significant amount of proteins, which, in turn, leads to a variety of possible gene mutations and genetic causes themselves. As a result of gene mutation, the following changes in membrane protein structures become possible:

decrease in the number of synthesized insulin receptors:

synthesis of a receptor with a modified structure;

disturbances in the system of glucose transport into the cell (GLUT proteins);

disturbances in the signal transmission system from the receptor to the cell:

changes in the activity of key enzymes of intracellular glucose metabolism - glycogen synthetase and pyruvate dehydrogenase.

The final result of these modifications is the formation of IR.

Mutations in the genes of proteins that transmit the insulin signal, insulin receptor substrate protein, glycogen synthetase, hormone-sensitive lipase, p3-adrenergic receptors, tumor necrosis factor a (TNF-a), etc. are identified as being of primary importance in the development of Ig.

In the development of disturbances in appetite regulation processes in the hypothalamus The role of leptin, a protein hormone secreted by adipocytes, has been most studied. The main effect of leptin is to suppress appetite and increase energy expenditure. It is carried out through a decrease in the production of neuropeptide-Y in the hypothalamus. A direct effect of leptin on taste cells has been revealed, leading to inhibition of feeding activity. A decrease in leptin activity in relation to the regulatory center of the hypothalamus is closely related to visceral obesity, which is accompanied by relative resistance of the hypothalamus to the central action of the hormone and, as a consequence, excess nutrition and disturbances in its usual diet.

Aging (over 40 years of age) and visceral obesity play an important role in the development leading to insulin resistance hormonal disorders, manifested:

an increase in the concentrations of testosterone, androstenedione and a decrease in progesterone in women;

decreased testosterone in men;

decreased concentration of somatotropin;

hypercortisolism;

hypercatecholaminemia.

Adipose tissue has the ability to secrete a large number of biologically active substances, many of which can cause the development of IR. These include the so-called "adipocytokines": leptin, adipsin, protein acylation stimulator, adiponectin, TNF-a, C-reactive protein, interleukin-1 (IL-1), interleukin-6 (IL-6) and others. Increased body weight due to visceral adipose tissue leads to disturbances in the production of adipocytokines by adipose tissue. The mechanism of action of leptin has already been described above. As for other adipocytokines, their effects are very diverse and often synergistic.

For example, adipsin, in the absence of food intake, stimulates the hunger center in the hypothalamus, causing increased appetite, excess food consumption and weight gain.

The acylation stimulator protein, by activating glucose uptake by fat cells, stimulates the process of lipolysis, which, in turn, leads to stimulation of diacylglycerol acyltransferase, inhibition of lipase and an increase in triglyceride synthesis.

It was found that adiponectin deficiency, observed in obesity, causes IR, reduces the antiatherogenic properties of the cytokine and is associated with a decrease in insulin sensitivity in women with hyperandrogenemia.

With increasing body weight, the production of TNF-a sharply increases, which reduces the activity of insulin receptor tyrosine kinase, phosphorylation of its substrate and leads to inhibition of the expression of GLUT proteins of intracellular glucose transport. The synergism of this effect of TNF-a with IL-1 and IL-6 has been established. Together with IL-6 and C-reactive protein, TNF-a causes activation of coagulation.

The influence of aging (age over 40 years) as an internal cause of IR is closely interrelated and is mediated through the action of other causes and factors of MS: genetic defects, physical inactivity, excess body weight, hormonal disorders, chronic stress.

The mechanisms leading to the formation of IR during aging are mainly reduced to the following sequential changes. Aging, along with a decrease in physical activity, leads to a decrease in the production of growth hormone (GH). An increase in cortisol levels, caused by increased social and personal tension, which invariably accompanies the aging process, is also a factor in the decrease in GH production. An imbalance of these two hormones (decrease in GH and increase in cortisol) is the cause of the development of visceral obesity, which, in addition, is stimulated by excess nutrition. Visceral obesity and chronic stress-related increased sympathetic activity lead to increased levels of free fatty acids, which reduce cellular sensitivity to insulin.

Physical inactivity - as a risk factor that adversely affects tissue sensitivity to insulin, it is accompanied by a decrease in the translocation of glucose transport proteins (GLUT proteins) in myocytes. The last circumstance represents one of the mechanisms for the formation of IR. More than 25% of subjects leading a sedentary lifestyle exhibit insulin resistance.

Excessive nutrition and the accompanying violation of a diet adequate to the body’s needs (in particular, excessive consumption of animal fats) lead to structural changes in the phospholipids of cell membranes and inhibition of the expression of genes that control the transmission of the insulin signal into the cell. These disorders are accompanied by hypertriglyceridemia, leading to excessive lipid deposition in muscle tissue, which impairs the activity of carbohydrate metabolic enzymes. This mechanism of IR formation is especially pronounced in patients with visceral obesity.

Hereditary predisposition to IR and obesity, combined with physical inactivity and excess nutrition, creates a vicious circle of MS pathogenesis. Compensatory GI caused by IR leads to a decrease and subsequently blocks the sensitivity of insulin receptors. The consequence of this is the deposition of lipids and glucose from food by adipose tissue, which increases IR, and subsequently GI. Hyperinsulinemia has an inhibitory effect on lipolysis, which causes the progression of obesity.

Effects of chronic stress , as an external factor in the development of metabolic syndrome, is associated with activation of the sympathetic division of the autonomic nervous system and an increase in the concentration of cortisol in the blood. Sympathicotonia is one of the causes of the development of insulin resistance. This action is based on the ability of catecholamines to enhance lipolysis with an increase in the concentration of free fatty acids, which leads to the formation of IR. Insulin resistance, in turn, has a direct activating effect on the sympathetic division of the autonomic nervous system (ANS). Thus, a vicious circle is formed: sympathicotonia - increased concentration of free fatty acids (FFA) - insulin resistance - increased activity of the sympathetic division of the ANS. In addition, hypercatecholaminemia, by inhibiting the expression of GLUT proteins, leads to inhibition of insulin-mediated glucose transport.

Glucocorticoids reduce tissue sensitivity to insulin. This effect is realized through an increase in the amount of adipose tissue in the body due to increased accumulation of lipids and inhibition of their mobilization. A polymorphism in the glucocorticoid receptor gene was discovered, which is associated with increased cortisol secretion, as well as a polymorphism in the dopamine and leptin receptor genes, which is associated with increased activity of the sympathetic nervous system in MS. Feedback in the hypothalamic-pituitary-adrenal system becomes ineffective with polymorphism in the fifth locus of the glucocorticoid receptor gene. This disorder is accompanied by insulin resistance and abdominal obesity.

An increase in cortisol levels has both a direct and indirect (through a decrease in somatotropin levels) effect on the formation of visceral obesity, which leads to an increase in fatty acids and the development of insulin resistance.

Pathogenesis of metabolic syndrome.

Insulin resistance, the causes of which are described above, is the central link in the pathogenesis and the unifying basis of all manifestations of the metabolic syndrome.

The next link in the pathogenesis of MS is systemic hyperinsulinemia. On the one hand, GI is a physiological compensatory phenomenon aimed at maintaining normal glucose transport into cells and overcoming IR, and on the other hand, it plays a critical role in the development of metabolic, hemodynamic and organ disorders characteristic of MS.

The possibility of occurrence, as well as the forms of clinical manifestations of HI, are closely related to the presence of genetic conditioning or predisposition. Thus, in individuals who are carriers of a gene that limits the ability of pancreatic 3-cells to increase insulin secretion, IR leads to the development of type 2 diabetes mellitus (DM). In individuals who are carriers of a gene that controls Na + /K + -cell pump, HI is accompanied by the development of intracellular accumulation of Na and Ca and an increase in the sensitivity of cells to the action of angiotensin and norepinephrine. The end result of the above metabolic disorders is the development of arterial hypertension. The combination of HI with the predominance of primary hereditary changes in the lipid composition of the blood can stimulate the expression of the corresponding gene and initiate the occurrence. a phenotype characterized by an increase in the level of low-density lipoproteins (LDL) and a decrease in the level of high-density lipoproteins (HDL), which leads to the development of atherosclerosis and associated diseases of the body systems and, first of all, the circulatory system.

An important role in the development and progression of insulin resistance and associated metabolic disorders is played by abdominal adipose tissue, neurohumoral disorders accompanying abdominal obesity, and increased activity of the sympathetic nervous system.

The results of the Framingham Study, published in 1983, indicate that obesity is an independent risk factor for cardiovascular disease. In a prospective 26-year observation of 5209 men and women using regression analysis, it was found that an increase in initial body weight was a risk factor for the development of coronary heart disease (CHD), deaths from ischemic heart disease and heart failure, independent of age and blood cholesterol levels , smoking, systolic blood pressure (BP), left ventricular hypertrophy and impaired glucose tolerance.

The risk of developing cardiovascular diseases and non-insulin-dependent diabetes in obesity is determined not so much by the presence of obesity, but by its type.

Wagyu first drew attention to the connection between the nature of fat distribution and the possibility of developing atherosclerosis, arterial hypertension, non-insulin-dependent diabetes mellitus and gout in 1956. He proposed the currently accepted division of android (central, obesity of the upper half of the body, viscero-abdominal) and ganoid (mainly lower half of the body, gluteofemoral) obesity.

The central type of obesity usually develops after 30 years and is associated with disturbances in physiological feedback in the hypothalamic-pituitary-adrenal system: a decrease in the sensitivity of the hypothalamic-pituitary zone to the inhibitory effect of cortisol, due to age-related changes and chronic psycho-emotional stress. As a result, hypercortisolism develops. The clinical picture of abdominal obesity is similar to the distribution of adipose tissue in true Cushing's syndrome. A small but chronic excess of cortisol activates cortisol-dependent lipoprotein lipase on the capillaries of fat cells of the upper body, abdominal wall and visceral adipose tissue, which leads to increased fat deposition and hypertrophy of adipocytes in these areas. At the same time, an increased concentration of cortisol reduces tissue sensitivity to insulin, promotes the development of insulin resistance and compensatory GI, which stimulates lipogenesis (fat formation in response to its loss during lipolysis) and inhibits lipolysis (decomposition of fat with the release of fatty acids and glycerol). Glucocorticoids affect the centers that regulate appetite and the activity of the autonomic nervous system. Under the influence of glucocorticoids, the expression of genes responsible for adipogenesis occurs.

Visceral adipose tissue, in contrast to adipose tissue of other localizations, is richer innervated and has a wider network of capillaries directly connected to the portal system. Visceral adipocytes have a high density of p3-adrenergic receptors, receptors for cortisol and androgenic steroids and a relatively low density of insulin and p2_adrenergic receptors. This causes the high sensitivity of visceral adipose tissue to the lipolytic effect of catecholamines, which is greater than the lipogenesis-stimulating effect of insulin.

Based on the above anatomical and functional features of visceral adipose tissue, the portal theory of insulin resistance was formulated, suggesting that IR and associated manifestations are caused by an excessive supply of free fatty acids to the liver through the portal vein, which drains blood from visceral adipose tissue. This reduces the activity of insulin binding and degradation processes in hepatocytes and leads to the development of insulin resistance at the liver level and inhibition of the suppressive effect of insulin on glucose production by the liver. Once in the systemic circulation, FFAs contribute to impaired absorption and utilization of glucose in muscle tissue, causing peripheral insulin resistance.

The direct influence of FFAs formed during lipolysis on the functioning of enzymes and transport proteins involved in glucose metabolism and glycogen synthesis has been proven. In the presence of increased concentrations of FFA in the liver and muscles, the activity and sensitivity to insulin of the enzymes of glycolysis and glycogenesis decrease, and an increase in gluconeogenesis in the liver is observed. The clinical manifestation of these processes is an increase in glucose concentration (on an empty stomach), disruption of its transport and an increase in insulin resistance.

One of the important aspects of the pathogenesis of MS is its atherogenic potential, that is, the risk of developing cardiovascular complications caused by atherosclerosis.

The most typical disorders of lipid metabolism in MS are an increase in the concentration of triglycerides and a decrease in the concentration of high-density lipoprotein cholesterol (HDL-C) in the blood plasma. Less common is an increase in total cholesterol (TC) and LDL cholesterol. The removal of LDL from the blood is regulated by lipoprotein lipase (LPL). This enzyme is controlled by the concentration of insulin in the blood. With the development of obesity, type 2 diabetes and insulin resistance syndrome, LPL becomes resistant to the action of insulin. Excessive insulin stimulates the passage of LDL into the arterial wall and activates the uptake of cholesterol by monocytes. Insulin also stimulates the migration of smooth muscle cells into the intima and their proliferation. In the intima, smooth muscle cells with monocytes filled with cholesterol form foam cells, which leads to the formation of an atheromatous plaque. Promoting the formation of atherosclerotic

plaques, insulin prevents the possibility of its reverse development. Insulin also activates platelet adhesion and aggregation and their production of platelet-derived growth factors.

Arterial hypertension is often one of the first clinical manifestations of metabolic syndrome. The main hemodynamic disturbances in MS are an increase in circulating blood volume, cardiac output, and total peripheral vascular resistance.

The mechanisms by which insulin resistance leads to the development of hypertension are not fully understood. It is assumed that insulin acts on cell membrane channels that regulate the flow of sodium and calcium into the cell. Intracellular calcium is one of the factors that determines the tension and contractility of vascular myocytes in response to the action of vasoconstrictor factors. It has been proven that the entry of calcium into smooth muscle cells and platelets under the influence of insulin is reduced. In IR, insulin is unable to reduce the influx of calcium into cells, which likely plays a role in the development of hypertension.

Hyperinsulinemia, being one of the leading factors in increasing blood pressure in MS, leads to the following effects:

increased activity of the sympathetic nervous system;

activation of the reabsorption of sodium and water in the kidney tubules, which leads to an increase in the volume of circulating blood;

stimulation of the transmembrane exchange of sodium and hydrogen ions, leading to the accumulation of sodium in vascular smooth muscle cells, increasing their sensitivity to endogenous pressor agents (norepinephrine, angiotensin-2, etc.) and increasing peripheral vascular resistance;

modulation of a 2 -adrenergic impulse transmission at the level of the vascular wall;

remodeling of the vascular wall by stimulating the proliferation of smooth muscle cells.

An increase in the activity of the sympathetic nervous system against the background of hyperinsulinemia is realized mainly through the central links of the sympathetic regulation of blood circulation - inhibition of the activity of α2-adrenergic receptors and Ij-imidazoline receptors. There is evidence of the prohypertensive role of leptin, realized through stimulation of sympathetic activity.

An increase in peripheral vascular resistance leads to a decrease in renal blood flow, causing activation of the renin-angiotensin-aldosterone system.

Vascular endothelial dysfunction makes an important contribution to the genesis of hypertension in metabolic syndrome. The endothelium is the “target organ” of insulin resistance. At the same time, the production of vasoconstrictors by the endothelium is enhanced, and the secretion of vasodilators (prostacyclin, nitric oxide) is reduced.

Violation of hemorheological properties of blood (increased fibrinogen content and increased activity of tissue plasminogen inhibitor) in combination with hyperlipidemia contributes to thrombus formation and disruption of microcirculation in vital organs. This contributes to early damage to such “target organs” of hypertension as the heart, brain, and kidneys.

Diagnostic algorithms.

The main symptoms and manifestations of metabolic syndrome are:

insulin resistance and hyperinsulinemia;

impaired glucose tolerance and type 2 diabetes;

arterial hypertension;

abdominal-visceral obesity;

dyslipidemia;

early atherosclerosis and ischemic heart disease;

hyperuricemia and gout;

hemostasis disorders;

microalbuminuria;

hyperandrogenism in women and decreased testosterone in men.

The given list is only of the main manifestations that are part of MS,

very extensive. However, to diagnose metabolic syndrome, there is no need to determine all of its components. This type of pathology is characterized by associations of clinical manifestations that differ in the composition of the components. The interaction of various genetic causes and risk factors leads to a certain partial phenotype of metabolic syndrome, characterized by a peculiar combination of symptoms, syndromes and diseases.

The main task of diagnosing MS is to identify the initial markers of the syndrome and order additional studies to detect latent metabolic disorders. The earliest manifestations of MS are dyslipidemia, hypertension, various laboratory markers of IR, and visceral obesity.

Today, the leaders in mortality are diseases of the cardiovascular system (stroke, myocardial infarction) and type 2 diabetes, so humanity has been fighting these diseases for a long time and persistently. The basis of preventive measures against any disease is the elimination of risk factors.

Metabolic syndrome is a term used in medical practice for the early detection and management of risk factors for diabetes and cardiovascular disease. At its core, metabolic syndrome is a group of risk factors for diabetes and cardiovascular diseases.

Disorders included in the metabolic syndrome remain undetected for a long time. Often they begin to form in childhood or adolescence and form the causes of diabetes, atherosclerotic diseases, and arterial hypertension.

Often in obese patients; slightly elevated blood glucose levels; Blood pressure that is at the upper limit of normal is not given due attention. The patient receives medical attention only when the risk criteria lead to the development of a serious illness.

It is important that such factors are identified and corrected as early as possible, and not when cardiac arrest looms on the horizon.

For the convenience of practicing doctors and patients themselves, clear criteria have been established, thanks to which it has become possible to make a diagnosis of “metabolic syndrome” with minimal examination.

Today, most medical specialists use a single definition that characterizes metabolic syndrome in women and men.

It was proposed by the International Diabetes Federation: a combination of abdominal obesity with any two additional criteria (arterial hypertension, impaired carbohydrate metabolism, dyslipidemia).

Symptomatic signs

First, it’s worth taking a closer look at metabolic syndrome, its criteria and symptoms.

The main and mandatory indicator is abdominal obesity. What it is? With abdominal obesity, adipose tissue is deposited mainly in the abdominal area. This kind of obesity is also called “android” or “apple-type.” It is important to note and.

“Gynoid” or “pear-type” obesity is characterized by the deposition of fatty tissue in the thighs. But this type of obesity does not have such serious consequences as the previous one, therefore it does not apply to the criteria for metabolic syndrome and will not be considered in this topic.

To determine the degree of abdominal obesity, you need to take a centimeter and measure your waist circumference at the middle of the distance between the ends of the iliac bones and costal arches. A Caucasian man's waist circumference of more than 94 cm is an indicator of abdominal obesity. A woman’s waist circumference is more than 80 cm, which signals the same thing.

Obesity rates for the Asian nation are more severe. For men, the permissible volume is 90 cm, for women it remains the same - 80 cm.

Note! The cause of obesity can be not only overeating and poor lifestyle. This pathology can be caused by serious endocrine or genetic diseases!

Therefore, if the symptoms listed below are present individually or in combination, you should contact a medical center as soon as possible for examination by an endocrinologist, who will rule out or confirm secondary forms of obesity:

• dry skin;
• swelling;
• bone pain;
• constipation;
• stretch marks on the skin;
• visual impairment;
• changes in skin color.

Other criteria:

1. Arterial hypertension - pathology is diagnosed if systolic blood pressure is equal to or exceeds 130 mm Hg. Art., and diastolic equals or exceeds 85 mm Hg. Art.
2. Lipid spectrum disorders. To determine this pathology, a biochemical blood test will be required, which is necessary to determine the level of cholesterol, triglycerides and high-density lipoproteins. The criteria for the syndrome are defined as follows: triglycerides more than 1.7 mmol/l; the high-density lipoprotein level is less than 1.2 mmol in women and less than 1.03 mmol/l in men; or established fact of treatment of dyslipidemia.
3. Disorders of carbohydrate metabolism. This pathology is evidenced by the fact that the fasting blood sugar level exceeds 5.6 mmol/l or the use of hypoglycemic drugs.

Establishing diagnosis

If the symptoms are vague and the pathology is not clear, the attending physician prescribes an additional examination. Diagnosis of metabolic syndrome is as follows:

• ECG study;
• daily blood pressure monitoring;
• Ultrasound of blood vessels and heart;
• determination of blood lipid levels;
• determination of blood sugar 2 hours after eating;
• study of kidney and liver function.

How to treat

First of all, the patient must radically change his lifestyle. In second place is drug therapy.

Lifestyle changes mean:

• changes in diet and nutrition;
• rejection of bad habits;
• increased physical activity during physical inactivity.

Without following these rules, drug treatment will not bring tangible results.

Very strict diets and, especially, fasting for metabolic syndrome are not recommended. Body weight should decrease gradually (5-10% in the first year). If the weight decreases rapidly, it will be very difficult for the patient to maintain it at the achieved level. In most cases, the kilograms lost suddenly come back again.

Changing your diet will be much healthier and more effective:

• replacing animal fats with vegetable fats;
• increasing the amount of fiber and plant fiber;
• reducing salt intake.

Carbonated drinks, fast food, confectionery, and white bread should be excluded from the diet. Vegetable soups should predominate, and lean varieties of beef are used as meat products. Poultry and fish should be steamed or boiled.

For cereals, it is recommended to use buckwheat and oatmeal; rice, millet, and pearl barley are allowed. But it is advisable to limit semolina or eliminate it completely. You can clarify so that everything is calculated correctly.

Nutritionists advise consuming vegetables such as beets, carrots, and potatoes no more than 200 grams. in a day. But zucchini, radishes, lettuce, cabbage, bell peppers, cucumbers and tomatoes can be eaten without restrictions. These vegetables are rich in fiber and therefore very healthy.

You can eat berries and fruits, but not more than 200-300 grams. in a day. Milk and dairy products should have minimal fat content. You can eat 1-2 glasses of cottage cheese or kefir a day, but heavy cream and sour cream should be consumed only occasionally.

For drinks, you can drink weak coffee, tea, tomato juice, juices and compotes from sour fruits without sugar and preferably homemade.

What kind of physical activity should you have?

It is recommended to increase physical activity gradually. In case of metabolic syndrome, preference should be given to running, walking, swimming, and gymnastics. It is important that the loads are regular and compared with the patient’s capabilities.

Treatment with drugs

In order to cure the syndrome, you need to get rid of obesity, arterial hypertension, carbohydrate metabolism disorders, and dyslipidemia.

Today, metabolic syndrome is treated with metformin, the dose of which is adjusted to control blood glucose levels. Usually at the beginning of treatment it is 500-850 mg.

Note! The drug is prescribed to elderly people with caution, and metformin is contraindicated for patients with impaired liver and kidney function.

Usually the drug is well tolerated, but side effects in the form of gastrointestinal disorders are still present. Therefore, it is recommended to take metformin after or during meals.

If the diet is violated or if the drug is overdosed, hypoglycemia may develop. Symptoms of the condition are expressed by trembling and weakness throughout the body, anxiety, and a feeling of hunger. Therefore, blood glucose levels must be carefully monitored.

Ideally, the patient should have a glucometer at home, which allows him to regularly monitor his blood sugar levels at home; for example, this can be used.

Orlistat (Xenical) is quite popular in the treatment of obesity today. Take it no more than three times a day, during the main meal.

If the food in your diet is not fatty, you can skip taking the drug. The action of the drug is based on reducing the absorption of fats in the intestines. For this reason, if you increase fat in your diet, unpleasant side effects may occur:

• frequent urge to defecate;
• flatulence;
• oily flow from the anus.

Patients with dyslipidemia, if long-term diet therapy is ineffective, are prescribed lipid-lowering drugs from the groups of fibrates and statins. These medications have significant limitations and serious side effects when used. Therefore, only the attending physician should prescribe them.

Drugs that lower blood pressure used for metabolic syndrome contain angiotensin-converting enzyme inhibitors (lisinopril, enalapril), imidosaline receptor agonists (moxonidine, rilmenidine), calcium channel blockers (amlodipine).

Catad_tema Metabolic syndrome - articles

Metabolic syndrome - the basics of pathogenetic therapy

T. V. Adasheva, Candidate of Medical Sciences, Associate Professor
O. Yu. Demicheva
Moscow State Medical and Dental University
City Clinical Hospital No. 11

In 1948, the famous clinician E.M. Tareev wrote: “The idea of ​​hypertension is most often associated with an obese hypersthenic person, with a possible disorder of protein metabolism, with blood clogging with products of incomplete metamorphosis - cholesterol, uric acid...” Thus, more than 50 years ago, the concept of metabolic syndrome (MS) was practically formed. In 1988, G. Reaven described a symptom complex including hyperinsulinemia, impaired glucose tolerance, low HDL cholesterol and arterial hypertension, giving it the name “syndrome X” and for the first time suggesting that insulin resistance (IR) with compensatory hyperinsulinemia. In 1989, J. Kaplan showed that an essential component of the “deadly quartet” is abdominal obesity. In the 90s the term “metabolic syndrome” appeared, proposed by M. Henefeld and W. Leonhardt. The prevalence of this symptom complex is becoming epidemic and in some countries, including Russia, reaches 25-35% among the adult population.

Generally accepted criteria for MS have not yet been developed, presumably due to the lack of common views on its pathogenesis. The ongoing discussion about the validity of using the terms “complete” and “incomplete” MS illustrates the underestimation of a single mechanism that determines the parallel development of all cascades of metabolic disorders in insulin resistance.

IR is a polygenic pathology, in the development of which mutations in the insulin receptor substrate genes (IRS-1 and IRS-2), β 3 -adrenergic receptors, uncoupling protein (UCP-1), as well as molecular defects in proteins of the insulin signaling pathway (glucose transporters) may play a role. ). A special role is played by a decrease in insulin sensitivity in muscle, fat and liver tissues, as well as in the adrenal glands. In myocytes, the supply and utilization of glucose is impaired, and resistance to the antilipolytic action of insulin develops in adipose tissue. Intensive lipolysis in visceral adipocytes leads to the release of large amounts of free fatty acids (FFA) and glycerol into the portal circulation. Entering the liver, FFAs, on the one hand, become a substrate for the formation of atherogenic lipoproteins, and on the other hand, they prevent the binding of insulin to the hepatocyte, potentiating IR. Hepatocyte IR leads to a decrease in glycogen synthesis, activation of glycogenolysis and gluconeogenesis. For a long time, IR is compensated by excess insulin production, so the violation of glycemic control does not manifest itself immediately. But, as the function of pancreatic β-cells is depleted, decompensation of carbohydrate metabolism occurs, first in the form of impaired fasting glycemia and glucose tolerance (IGT), and then type 2 diabetes mellitus (T2DM). An additional decrease in insulin secretion in MS is caused by long-term exposure of β-cells to high concentrations of FFA (the so-called lipotoxic effect). With existing genetically determined defects in insulin secretion, the development of T2DM is significantly accelerated.

According to another hypothesis, abdominal adipose tissue plays a leading role in the development and progression of insulin resistance. A feature of visceral adipocytes is their high sensitivity to the lipolytic action of catecholamines and low sensitivity to the antilipolytic action of insulin.

In addition to substances that directly regulate lipid metabolism, the fat cell produces estrogens, cytokines, angiotensinogen, plasminogen activator inhibitor-1, lipoproten lipase, adipsin, adinopectin, interleukin-6, tumor necrosis factor-α (TNF-α), transforming growth factor B, leptin etc. It has been shown that TNF-α is able to act on the insulin receptor and glucose transporters, potentiating insulin resistance, and stimulating leptin secretion. Leptin (“the voice of adipose tissue”) regulates eating behavior by affecting the hypothalamic satiety center; increases the tone of the sympathetic nervous system; enhances thermogenesis in adipocytes; suppresses insulin synthesis; affects the cell's insulin receptor, reducing glucose transport. In obesity, leptin resistance is observed. It is believed that hyperleptinemia has a stimulating effect on some hypothalamic releasing factors (RF), in particular ACTH-RF. Thus, with MS, mild hypercortisolism is often observed, which plays a certain role in the pathogenesis of MS.

Particular attention should be paid to the mechanisms of development of arterial hypertension (AH) in MS; some of them were unknown until recently, which is why the pathogenetic approach to the treatment of MS was not fully developed.

There are numerous studies devoted to the study of the subtle mechanisms of the influence of insulin resistance and hyperinsulinemia on blood pressure levels.

Normally, insulin has a vascular protective effect due to the activation of phosphatidyl 3-kinase in endothelial cells and microvessels, which leads to expression of the endothelial NO synthase gene, release of NO by endothelial cells and insulin-mediated vasodilation.

Currently, the following mechanisms of the effect of chronic hyperinsulinemia on blood pressure have been established:

• stimulation of the sympathoadrenal system (SAS);
• stimulation of the renin-angiotensin-aldosterone system (RAAS);
• blockade of transmembrane ion exchange mechanisms with an increase in the content of intracellular Na+ and Ca++, a decrease in K+ (increased sensitivity of the vascular wall to pressor influences);
• increased reabsorption of Na+ in the proximal and distal tubules of the nephron (fluid retention with the development of hypervolemia), retention of Na+ and Ca++ in the walls of blood vessels with an increase in their sensitivity to pressor influences;
• stimulation of proliferation of smooth muscle cells of the vascular wall (narrowing of arterioles and increasing vascular resistance).

Insulin is involved in regulating the activity of the sympathetic nervous system in response to food intake. Experimental studies have found that during fasting, SAS activity decreases, and when food is consumed, it increases (especially fats and carbohydrates).

It is assumed that insulin, passing through the blood-brain barrier, stimulates glucose uptake in regulatory cells associated with the ventromedial nuclei of the hypothalamus. This reduces their inhibitory effect on the centers of the sympathetic nervous system of the brain stem and increases the activity of the central sympathetic nervous system.

Under physiological conditions, this mechanism is regulatory, but with hyperinsulinemia it leads to persistent activation of the SAS and stabilization of hypertension.

Increased activity of the central parts of the SAS leads to peripheral hypersympathicotonia. In the kidneys, activation of JGA β-receptors is accompanied by the production of renin, and sodium and fluid retention increases. Persistent hypersympathicotonia in the periphery of skeletal muscles leads to disruption of the microvasculature, first with physiological rarefaction of microvessels, and then to morphological changes, such as a decrease in the number of functioning capillaries. A decrease in the number of adequately supplied myocytes, which are the main consumer of glucose in the body, leads to an increase in insulin resistance and hyperinsulinemia. Thus, the vicious circle closes.

Insulin, through mitogen-activated protein kinase, enhances the damaging vascular effects due to the stimulation of various growth factors (platelet growth factor, insulin-like growth factor, transforming growth factor P, fibroblast growth factor, etc.), which leads to proliferation and migration of smooth muscle cells, proliferation of vascular fibroblasts walls, accumulation of extracellular matrix. These processes cause remodeling of the cardiovascular system, leading to loss of elasticity of the vascular wall, disruption of microcirculation, progression of atherogenesis and, ultimately, an increase in vascular resistance and stabilization of hypertension.

Some authors believe that endothelial dysfunction plays a major role in the pathogenesis of hypertension associated with metabolic disorders. In individuals with insulin resistance and hyperinsulinemia, there is a decrease in response to vasodilation and an increase in response to vasoconstriction, which leads to cardiovascular complications.

Metabolic syndrome is characterized by hyperuricemia (according to various sources, it occurs in 22-60% of patients with MS).

It has now been shown that the concentration of uric acid in the blood correlates with triglyceridemia and the severity of abdominal obesity; This phenomenon is based on the fact that increased fatty acid synthesis activates the pentose pathway of glucose oxidation, promoting the formation of ribose-5-phosphate, from which the purine core is synthesized.

Taking into account all the aspects of the problem discussed above, a therapeutic algorithm for a pathogenetic approach to the treatment of metabolic syndrome should be formed.

Treatment of metabolic syndrome

The complex of treatment for metabolic syndrome includes the following equivalent items: lifestyle changes, treatment of obesity, treatment of carbohydrate metabolism disorders, treatment of arterial hypertension, treatment of dyslipidemia.

Lifestyle change

This aspect underlies the successful treatment of metabolic syndrome.

The doctor’s goal in this case is to form a stable motivation in the patient, aimed at long-term implementation of recommendations on nutrition, physical activity, and taking medications. A “success mindset” allows the patient to more easily endure the hardships that lifestyle changes require.

Changing your diet. The diet of a patient with metabolic syndrome should not only ensure weight loss, but also not cause metabolic disorders and provoke an increase in blood pressure. Fasting in syndrome X is contraindicated, as it is severe stress, and with existing metabolic disorders, it can lead to acute vascular complications, depression, and a breakdown in a “food binge.” Meals should be frequent, food should be taken in small portions (usually three main meals and two or three intermediate meals) with a daily calorie content of no more than 1500 kcal. The last meal is an hour and a half before bedtime. The basis of nutrition is complex carbohydrates with a low glycemic index; they should account for up to 50–60% of the nutritional value. The glycemic index unit of a food is the change in glycemia after a meal equal to the change in glycemia after consuming 100 g of white bread. Most confectionery products, sweet drinks, baked goods, and small cereals have a high glycemic index; their consumption should be eliminated or reduced to a minimum. Low GI in whole grains, vegetables, fruits rich in dietary fiber. The total amount of fat should not exceed 30% of the total calorie content, saturated fat - 10%. Each meal should include an adequate amount of protein to stabilize glycemia and promote satiety. You should eat fish at least twice a week. Vegetables and fruits should be present in the diet at least five times a day. The permissible amount of sweet fruits depends on the degree of carbohydrate metabolism disorder; in the presence of type 2 diabetes mellitus, they should be sharply limited.

Table salt - no more than 6 g per day (one teaspoon).

Alcohol, as a source of “empty calories”, an appetite stimulant, and a glycemic destabilizer, should be excluded from the diet or reduced to a minimum. If it is impossible to give up alcohol, preference should be given to dry red wine, no more than 200 ml per day.

Quitting smoking is necessary; this significantly reduces the risk of cardiovascular and cancer complications.

Physical activity. According to G. Reaven, insulin resistance can be found in 25% of people leading a sedentary lifestyle. Regular muscle activity itself leads to metabolic changes that reduce insulin resistance. To achieve a therapeutic effect, it is enough to practice 30 minutes of intense walking every day or 20-30 minutes of jogging three to four times a week.

Obesity treatment

When treating metabolic syndrome, a satisfactory result can be considered a reduction in weight by 10-15% in the first year of treatment, by 5-7% in the second year and the absence of relapses in body weight gain in the future.

Following a low-calorie diet and physical activity regimen is not always feasible for patients. In these cases, drug therapy for obesity is indicated.

Currently, the drugs orlistat and sibutramine are registered and recommended for long-term treatment of obesity in Russia. The mechanism of their action is fundamentally different, which makes it possible to select the optimal drug in each specific case, and in severe cases of obesity that are resistant to monotherapy, prescribe these drugs in a complex manner.

Treatment of carbohydrate metabolism disorders

The severity of carbohydrate metabolism disorders in metabolic syndrome ranges from minimal (impaired fasting glycemia and glucose tolerance (IGT)) to the development of type 2 diabetes mellitus.

In the case of metabolic syndrome, medications that affect carbohydrate metabolism should be prescribed not only in the presence of T2DM, but also in less severe (reversible!) disorders of carbohydrate metabolism. Hyperinsulinemia requires aggressive therapeutic tactics. There is evidence of the presence of complications characteristic of diabetes mellitus already at the stage of impaired glucose tolerance. This is believed to be due to frequent episodes of postprandial hyperglycemia.

A powerful arsenal of modern hypoglycemic agents allows you to choose the optimal therapy in each specific case.

1. Drugs that reduce insulin resistance

For metabolic syndrome - drugs of choice.

A. Biguanides

Currently, the only biguanide that reduces insulin resistance is metformin. According to the UKPDS results, treatment with metformin in T2DM reduces the risk of death from diabetes by 42%, myocardial infarction by 39%, and stroke by 41%.

Mechanism of action: increasing tissue sensitivity to insulin; suppression of gluconeogenesis in the liver; changing the pharmacodynamics of insulin by reducing the ratio of bound to free insulin and increasing the ratio of insulin to proinsulin; suppression of fat oxidation and formation of free fatty acids, reduction of triglycerides and LDL, increase of HDL; according to some data - a hypotensive effect; stabilization or reduction of body weight. Reduces fasting hyperglycemia and postprandial hyperglycemia. Does not cause hypoglycemia.

It can be prescribed for IGT, which is especially important from the point of view of preventing the development of T2DM.

B. Thiazolidinediones (“glitazones”, insulin sensitizers)

Pioglitazone and rosiglitazone are approved for clinical use.

In Russia, this is a rarely used group of drugs, probably due to their relative novelty, the known risk of acute liver failure and high cost.

Mechanism of action: increase glucose uptake by peripheral tissues (activate GLUT-1 and GLUT-4, suppress the expression of tumor necrosis factor, which increases insulin resistance); reduce glucose production by the liver; reduce the concentration of free fatty acids and triglycerides in plasma by suppressing lipolysis (through increasing the activity of phosphodiesterase and lipoprotein lipase). They act only in the presence of endogenous insulin.

2. α-glucosidase inhibitors

Acarbose drug

Mechanism of action: competitively inhibits intestinal α-glucosidases (sucrase, maltase, glucoamylase) - enzymes that break down complex sugars. Prevents the absorption of simple carbohydrates in the small intestine, which leads to a decrease in postprandial hyperglycemia. Reduces body weight and, as a result, has a hypotensive effect.

3. Insulin secretogens

Drugs of this class are prescribed for metabolic syndrome in cases where it is not possible to achieve satisfactory glycemic control with the help of drugs that reduce insulin resistance and/or acarbose, as well as in the presence of contraindications to them. The risk of developing hypoglycemia and weight gain with long-term use requires a strictly differentiated approach when choosing a drug. Prescription for NTG is not practiced. The combination of insulin secretogens with biguanides is very effective.

A. Sulfonylureas

Clinical experience shows that monotherapy with some insulin secretogens (in particular, glibenclamide) in patients with metabolic syndrome usually turns out to be ineffective even in maximum doses due to increasing insulin resistance - the secretory capacity of β-cells is depleted and an insulin-requiring variant of T2DM is formed. Preference should be given to highly selective dosage forms that do not cause hypoglycemia. It is desirable that the drug can be taken once a day to increase treatment compliance.

These requirements are met by the second generation drug gliclazide in the pharmacological form of MV (modified release) and the third generation drug glimepiride.

Gliclazide - a highly selective drug (specific to the SUR1 subunit of ATP-sensitive potassium channels of β-cells), restores the physiological profile of insulin secretion; increases the sensitivity of peripheral tissues to insulin, causing post-transcriptional changes in GLUT-4 and activating the action of insulin on muscle glycogen synthetase; reduces the risk of thrombosis by inhibiting platelet aggregation and adhesion and increasing the activity of tissue plasminogen; reduces the level of lipid peroxides in plasma.

Glimepiride complexes with the sulfonylurea receptor SURX. Has a pronounced peripheral effect: increases the synthesis of glycogen and fat by activating the translocation of GLUT-1 and GLUT-4; reduces the rate of gluconeogenesis in the liver, increasing the content of fructose-6-biphosphate. It has lower glucagonotropic activity than other sulfonylurea drugs. Provides a low risk of hypoglycemia - causes a maximum decrease in blood glucose with minimal insulin secretion. It has antiaggregation and antiatherogenic effects, selectively inhibiting cyclooxygenase and reducing the conversion of arachidonic acid to thromboxane A2. It is complexed with caveolin in fat cells, which probably determines the specificity of the effect of glimepiride on the activation of glucose utilization in adipose tissue.

B. Prandial glycemic regulators (short-acting secretogens)

Fast-acting hypoglycemic drugs, amino acid derivatives. In Russia they are represented by repaglinide and nateglinide.

Mechanism of action- rapid, short-term stimulation of insulin secretion by the β-cell due to rapid reversible interaction with specific receptors of ATP-sensitive potassium channels.

It is believed that nateglinide is safer with respect to the development of hypoglycemia: insulin secretion caused by nateglinide depends on the level of glycemia and decreases as the level of glucose in the blood decreases. The possibility of using low doses of nateglinide for IGT in patients at high risk of cardiovascular complications is being studied (NAVIGATOR).

4. Insulin therapy

Early initiation of insulin therapy for metabolic syndrome (except in cases of decompensated diabetes) seems undesirable, as it is likely to aggravate the clinical manifestations of hyperinsulinism. However, it should be noted that, in order to avoid complications of diabetes mellitus, compensation of carbohydrate metabolism must be achieved at any cost. If the effect of the previously listed types of treatment is unsatisfactory, insulin therapy should be prescribed, possibly in acceptable combinations with oral hypoglycemic drugs. In the absence of contraindications, combination with biguanides is preferable.

Treatment of arterial hypertension

Target blood pressure level for the development of type 2 diabetes mellitus -< 130/85 мм рт. ст.; при нарушении функции почек - < 125/75 мм рт. ст.

An ideal antihypertensive drug in this clinical situation should have a proven effect on cardiovascular end points, not have negative metabolic effects, affect the pathogenetic links of hypertension in insulin resistance and have a number of protective effects (cardio-, nephro-, vasoprotection) with a beneficial effect on endothelial function, platelet-vascular hemostasis and fibrinolysis.

ACE inhibitors

ACE inhibitors are the drugs of choice in the clinical group under discussion. This is due, firstly, to the pathogenetic validity of their use (activation of the RAAS in IR) and, secondly, to a number of advantages of drugs of this class:

• reducing insulin resistance and improving glycemic control;
• no negative effect on lipid and purine metabolism (FASET, ABCD, CAPPP, HOPE, UKPDS);
• vasoprotective effect - regression of vascular remodeling; anti-atherosclerotic effect (SECURE - HOPE-substudy);
• nephroprotective effect in diabetic and non-diabetic forms of nephropathy (FACET, MICRO-HOPE, REIN, EUCLID, AIPRI, BRILLIANT);
• correction of endothelial dysfunction, beneficial effects on platelet hemostasis and fibrinolysis: NO, prostacyclin, ↓endothelin, endothelium-dependent hyperpolarization factor, ↓procoagulant potential, tissue plasminogen activator, ↓platelet aggregation (TREND).

Thus, ACE inhibitors meet all the requirements for an antihypertensive drug for patients with metabolic syndrome.

β-blockers

Prescribing β-blockers to patients with metabolic syndrome has an undeniable pathogenetic advantage due to the presence of hypersympathocotonia, the mechanisms of which were discussed above. However, for a long time in this clinical group, these drugs were prescribed taking into account a number of restrictions; it was also believed that they were contraindicated for patients with diabetes mellitus due to their negative effect on carbohydrate and lipid metabolism.

However, the results of UKPDS and other studies have proven the effectiveness and safety of the use of selective beta-blockers in patients with metabolic disorders and type 2 diabetes. All adverse side effects were mainly associated with the use of non-selective and low-selective β-blockers.

Thus, in patients with metabolic syndrome, it is possible to use highly selective β-blockers (betaxolol, bisoprolol, nebivolol, etc.) as part of combination therapy in small doses.

Diuretics

Along with β-blockers, thiazide and thiazide-like diuretics are considered first-line drugs for long-term treatment of patients with uncomplicated hypertension. However, as in the case of β-blockers, the use of drugs in this group has a number of limitations due to the development of side effects: decreased sensitivity of peripheral tissues to insulin with compensatory hyperinsulinemia, increased glycemia, adverse effects on the lipid profile (increased triglycerides in the blood , total cholesterol, low-density lipoprotein cholesterol), impaired uric acid metabolism (hyperuricemia).

Many multicenter prospective studies have noted a high incidence of diabetes mellitus in patients with hypertension when treated with thiazide and thiazide-like diuretics. The thiazide-like diuretic indapamide, which combines the properties of a diuretic and a vasodilator, has a lesser effect on metabolic risk factors. According to the literature, with long-term therapy, indapamide does not have a negative effect on carbohydrate and lipid metabolism and does not worsen renal hemodynamics, which makes it the drug of choice in this clinical group.

Calcium antagonists

Currently, many years of discussion about the effectiveness and safety of calcium antagonists have been summed up.

Numerous multicenter studies have proven a reduction in the risk of cardiovascular complications (STOP-2, NORDIL, INSIGHT, VHAT, NICS-EH, HOT, ALLHAT) during therapy with these drugs. In addition, calcium antagonists have a number of advantages that justify their use in patients with metabolic syndrome:

• decreased insulin resistance, decreased basal and glucose-stimulated insulin levels;
• no negative impact on carbohydrate and lipid purine metabolism;
• vasoprotective effect - regression of vascular remodeling, anti-atherosclerotic effect (INSIGHT, MIDAS, ELSA);
• nephroprotective effect (proven for non-hydropyridine drugs);
• correction of endothelial dysfunction - an increase in NO due to antioxidant mechanisms (superoxide dismutase activity, ↓NO destruction), improvement of platelet-vascular and fibrinolytic components of hemostasis (↓platelet aggregation, ↓thrombomodulin).

Preference should be given to long-acting non-hydropyridine and dihydropyridine drugs due to the ability of short-acting calcium antagonists, prescribed in large doses, to increase the risk of cardiovascular complications.

AT 1-angiotensin receptor blockers

At the present stage, this group of drugs is one of the most actively studied.

A reduction in the risk of cardiovascular complications in patients with hypertension during treatment with losartan was shown in the LIFE study. Proven nephroprotective effect for diabetic nephropathy in T2DM (RENALL, IDNT, CALM). In addition, the ability of AT 1-angiotensin receptor blockers to reduce uric acid levels (losartan) has been shown.

The influence of AT 1 -angiotensin receptor blockers on the pathogenetic links of hypertension in metabolic syndrome and the absence of a negative effect on carbohydrate and lipid metabolism make these drugs promising in this clinical group. A multicenter study evaluating the effect of valsartan on cardiovascular events in patients with impaired carbohydrate tolerance (NAVIGATOR) is currently underway. Further study of this group of drugs may place them on par with ACE inhibitors when it comes to the treatment of metabolic syndrome.

α 1 -blockers

Until the interim analysis of the ALLHAT trial, which found an increase in cardiovascular events, particularly new cases of heart failure, with doxazosin, drugs in this group were considered among the most promising drugs used to treat patients with metabolic syndrome. This is due to the ability of α-blockers to increase tissue sensitivity to insulin and, as a result, improve glycemic control, correct the lipid profile, and have a beneficial effect on hemostasis and endothelial function.

However, at this stage, α 1 -blockers can only be used as additional drugs in combination therapy for hypertension, including metabolic syndrome.

I 1 -imidazoline receptor agonists

Drugs of this group occupy a special place in the treatment of metabolic syndrome due to the correction of one of the main links in the pathogenesis of hypertension - central hypersympathicotonia. These drugs, by reducing central sympathetic impulses, increase the sensitivity of peripheral tissues to insulin, improve glycemic control and reduce the activity of the RAAS.

Unfortunately, there is no data on the effect of I 1 -imidazoline receptor agonists on the prognosis of patients with hypertension, which does not allow recommending drugs of this class as first-line agents in the treatment of hypertension. However, they can be successfully used in combination therapy.

Treatment of dyslipidemia

Lipid-lowering therapy must be carried out in patients with MS and combined with therapeutic effects on IR and glycemia.

Statins are undoubtedly the first-line drugs in the treatment of dyslipidemia in patients with metabolic syndrome due to their good clinical efficacy (25-61% reduction in LDL, reduction in triglycerides) and good tolerability.

For isolated hypertriglyceridemia or severe hypertriglyceridemia, the drugs of choice are fibrates, which are inferior to statins in their effect on LDL, are less well tolerated and interact with a large number of drugs. The DAIS and VA HIT studies also demonstrated the beneficial effects of fibrates on cardiovascular risk in T2DM.

Conclusion

Thus, considering MS as a “generalized cardiovascular-metabolic disease” (the term of L. M. Resnick), we propose to focus on pathogenetic approaches to its treatment. It is also important to develop uniform diagnostic criteria and include the diagnosis of “metabolic syndrome” in the list of Medical Economic Standards. From the point of view of evidence-based medicine, it is desirable to conduct targeted multicenter studies of drugs used to treat metabolic syndrome.

Formin(metformin) - Drug dossier