RU2457834C1 - Method of treating metabolic syndrome - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to endocrinology and cardiology and deals with treatment of metabolic syndrome. For this purpose complex treatment, which includes antihypertensive diet, individually selected aerobic physical exercise, introduction of metformin in dose 500 mg two days per day and melaxen, is carried out. Melaxen is introduced before going to bed 30 minutes before sleeping in dose 1-2 mg during first two weeks, and then in dose 3 mg during the following ten weeks. Course of treatment constitutes 12 weeks.

EFFECT: complex of non-pharmacological and pharmacological therapy as well as empirically selected mode of melaxen introduction ensure efficient treatment due to essential reduction of body weight and reduction of insulin-resistance in said group of patients.

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Description

The invention relates to medicine, namely to endocrinology and cardiology, and can be used to treat patients with metabolic syndrome.

Metabolic syndrome is a combination of abdominal obesity, insulin resistance and relative hyperinsulinemia, which cause the development of arterial hypertension, disorders of carbohydrate, lipid and purine metabolism (Oganov R.G. National clinical recommendations. Diagnosis and treatment of metabolic syndrome // R.G. Oganov, M .N. Mamedov. - M.: “MEDI Expo”, 2009. - P.255).

The role of the metabolic syndrome in the development of atherosclerosis and coronary heart disease, type 2 diabetes mellitus, obstructive sleep apnea syndrome, polycystic ovaries, liver steatosis and non-alcoholic steatohepatitis, renal dysfunction in the form of a decrease in glomerular filtration rate and the formation of microalbuminuria, leads to a decrease in the quality of life of patients and is the main cause of high mortality.

In modern recommendations for the treatment of metabolic syndrome, a complex of therapeutic measures is presented that affect the main pathogenesis links of this condition. It includes both non-pharmacological measures aimed at reducing body weight - adhering to a low-calorie diet, physical activity regimen, maintaining a food diary, and the use of pharmacological drugs, in order to correct insulin resistance, dyslipidemia, arterial hypertension and disorders of carbohydrate metabolism (Oganov R.G. National clinical recommendations. Diagnosis and treatment of metabolic syndrome // RG Oganov, MN Mamedov. - M.: MEDI Expo, 2009. - P.261-269). Nevertheless, the currently used treatment regimens for the metabolic syndrome do not allow achieving the desired result. Therefore, the development of effective methods of treating the metabolic syndrome is an urgent problem of modern medicine.

Conducted research on the medical-scientific and patent literature found various methods of treating the metabolic syndrome.

In the work of Houmard J.A. (Effects of exercise training on absolute and relative measurements of regional adiposity // Int. J. Obes. - 1994. - Vol.18. - P.243-248) describes a method of treating the metabolic syndrome, which consists in performing regular physical activity of 30 -40 minutes a day, 3-4 times a week, for 14 weeks.

The disadvantage of this method is the limitation of its scope, since physical activity cannot be prescribed for complications of the metabolic syndrome such as coronary heart disease and decompensation of type 2 diabetes. The use of physical activity is difficult in elderly patients. The disadvantage of monotherapy with physical activity is also the short-term effect of treatment and the appearance of clinically significant results no earlier than 30 days after the start of therapy.

Radack, C., Deck, C. (The Effects of Omega-3 Polyunsaturated Fatty Acids on Blood Pressure: A Methodologic Analysis of the Evidence // Journal of the American College of Nutrition. - 1989. - Vol.8 (5). - P.376-385) describes a method of treating the metabolic syndrome, which consists in prescribing a diet to patients with a restriction of saturated fatty acids with food and an increase in omega-3 polyunsaturated fatty acids.

The disadvantage of this method is the lack of effectiveness of the treatment, due to its effect on only one parameter of the metabolic syndrome - overweight or obesity. Therefore, this treatment method cannot be used in cases where the development of the metabolic syndrome is associated with the action of antibodies, endotoxins, lipid peroxidation products, and contra-hormonal hormones. The disadvantage of this method is to reduce the quality of life of patients, since compliance with the described diet requires patients to know and control the chemical composition of the products. In addition, the side effects of omega-3 polyunsaturated fatty acids include weight gain and hyperglycemia, which limits their use in patients with metabolic syndrome (VIDAL Handbook. Drugs of Russia // Yu. B. Belousov et al. - M .: AstraPharmService, 2009 .-- S.997).

In the patent of the Russian Federation No. 2132190 (published on June 27, 1999), a method of treating the metabolic syndrome is presented, which consists in administering the drug CINT at night to patients with early morning hypertension and in the morning to patients with daytime hypertension. The initial dose of the drug is 0.1 mg, and then 0.1-0.6 mg.

The disadvantage of this method is the limited scope of the drug CINT in patients with severe concomitant diseases, such as severe cardiac arrhythmias, heart failure, unstable angina, impaired liver and kidney function, impaired peripheral circulation (Russian Drug Register. Encyclopedia of drugs. / Edited by G.L. Vyshkovsky. - M.: Publishing House "RLS", 2009. - P.584).

In the patent of the Russian Federation No. 2143902 (published on January 10, 2000), a “Method for the treatment of metabolic syndrome X” is described. The method consists in conducting 5 plasmapheresis sessions with an interval of 2 days with the evacuation of 25% of the circulating plasma per session, with the preliminary introduction of physiological saline with antiplatelet trental and incomplete compensation of plasma loss by introducing 400 ml of saline with the addition of essential at a dose of 10 ml.

The disadvantages of this method are its invasiveness, as well as limited availability due to the possibility of its implementation only in a hospital. The limited use of plasmapheresis in the treatment of metabolic syndrome is also due to possible complications of this therapy in the form of bleeding and catheter infections. In addition, this method of treatment is symptomatic, since it does not affect the main pathogenesis of the metabolic syndrome - insulin resistance, and therefore has only a temporary and short-term effect.

RF patent No. 2338519 (published November 20, 2008) describes a method for treating the metabolic syndrome, which consists in prescribing an individually selected hypocaloric diet and administering metoprolol in a dose of 100 mg in the morning for 24 weeks.

The disadvantage of this method is an increase in insulin resistance, a deterioration in the glycemic profile, an increase in body weight, an increase in triglycerides, a decrease in the concentration of high density lipoprotein cholesterol, and an increase in low density lipoprotein cholesterol due to the use of low-selective β ₁ -adrenergic blocking agent (Cruickshank JM Beta-blockers continue to surprise us // Eur. Heart J. - 2000. - Vol.21, No. 5. - P.368; Sharma AM Hypothesis: beta-adrenergic receptor blockers and weight gain: a systematic analysis. / AMSharma [et aL] // Hypertension. - 2001. - Vol. 37, No. 2. - P.250-254; Jacob S. Metabolic properties of vasodilating beta blocker s: management considerations for hypertensive diabetic patients and patients with the metabolic syndrome. / S. Jacob, EJ Henriksen // J. Clin. Hypertens. (Greenwich). - 2004. - Vol.6, No. 12. - P.690-696 ) The use of this method is limited in elderly patients, as well as with a weakened allergic history, impaired liver and / or kidney function, is contraindicated for atrioventricular blockade of the second and third degree, acute and chronic heart failure, severe peripheral circulation disorders (Russian Drug Register. Encyclopedia of drugs / Edited by G.L. Vyshkovsky. - M.: Radar Publishing House, 2006. - P.506). The above undesirable effects may limit the use of this method for the treatment of metabolic syndrome.

The closest technical solution adopted for the prototype is a method of treating the metabolic syndrome described in William W. et al. (The effect of metformin and standard therapy versus standard therapy alone in nondiabetic patients with insulin resistance and nonalcoholic steatohepatitis (NASH): a pilot trial // Therapeutic Advances in Gastroenterology. - 2009. - Vol.2 (3). - P.157. -163), which consists in prescribing to patients during the course of treatment an antihypertensive diet, individually selected aerobic exercise for 30 minutes a day, four times a week, and metformin at a dose of 500 mg per day. The total duration of treatment is 12 months. According to the authors, as a result of the treatment, the body mass index decreases by 0.9 kg / m ² , and the Homeostasis Model Assessment (HOMA-IR) insulin resistance index decreases by 1.58.

The disadvantages of the prototype are the duration of treatment and its lack of effectiveness, consisting in an insufficient decrease in insulin resistance and body weight of the patient.

The aim of the present invention is to increase the efficiency and reduce the treatment of metabolic syndrome.

This goal is achieved by the fact that patients with metabolic syndrome are prescribed an antihypertensive diet, individually selected aerobic exercise and the drug metformin. Additionally, from the first day, the drug is administered melaxen at night 30 minutes before bedtime at a dose of 1-2 mg for the first two weeks of the course, at a dose of 3 mg for the next ten weeks. Metformin is prescribed 500 mg twice a day. The course of treatment is 12 weeks.

The drug is melaxen, the active substance is melatonin. Registration number: P N015325 / 01 from 08/29/2008. Pharmacotherapeutic group: adaptogenic agent. Melaxen is a synthetic analogue of the hormone of the pineal gland - the pineal gland, synthesized from amino acids of plant origin, penetrates well through the blood-brain barrier. Melaxen normalizes circadian rhythms; regulates the sleep-wake cycle, daily changes in locomotor activity and body temperature; contributes to the normalization of night sleep, reduces stress reactions; exhibits immunostimulating and pronounced antioxidant properties (Russian Medicines Register. Encyclopedia of drugs. / Edited by G.L. Vyshkovsky. - M.: Radar Publishing House, 2006. - P.490).

The introduction of melaxen into patients with metabolic syndrome reduces insulin resistance, accelerates weight loss, and normalizes carbohydrate and lipid metabolism. This is due to the activation of peripheral insulin receptors by phosphorylation of tyrosine kinase, as well as the restoration of the circadian rhythm of adipose tissue activity (Anhe GF In vivo activation of insulin receptor tyrosine kinase by melatonin in the rat hypothalamus. / GFAnhe [et al.] // J . Neurochem. - 2004. - Vol.90. - P.559-566; Mühlbauer E. Loss of melatonin signaling and its impact on circadian rhythms in mouse organs regulalating blood glucose. / E. Mühlbauer [et al.] // Eur J. Pharmacol. - 2009. - Vol. 606. - P.61-71; Wolden-Hanson T. Daily melatonin administration to middle-aged male rats suppresses body weight, intraabdominal adiposity, and plasma leptin and insulin independent of food intake and total body fat. / T. Wolden-Hanson [et al.] // Endocrinology. - 2000. - Vol. 141. - P.487-97).

Detailed description of the method.

Patients with metabolic syndrome are prescribed an antihypertensive diet (Your Guide to Lowering Your Blood Pressure With DASH // US Department of Health and Human Services. - NIH Publication No.06-4082, 2006. - P.8-12), individually selected aerobic physical load (Metabolic syndrome. / Edited by V. Fonseca. Translated from English. - M .: "Practice", 2011. - P.63-79) and the drug metformin. Additionally, from the first day, the drug is administered melaxen at night 30 minutes before bedtime at a dose of 1-2 mg, over the next ten weeks at a dose of 3 mg The initial dose of melaxen is selected individually, taking into account the patient's body weight and the initial figures of blood pressure. Two weeks after the start of treatment, the patient is transferred to the most effective therapeutic dose of melaxen - 3 mg per day at night 30 minutes before bedtime (Cagnacci A. Effect of exogenous melatonin on vascular reactivity and nitric oxide in postmenopausal women: role of hormone replacement therapy . / A. Cagnacci [et all.] // Clin. Endocrinol. - 2001. - Vol. 54. - P.261-266). Metformin is prescribed 500 mg twice a day, at lunch and in the evening during meals to reduce body weight and prevent the development of type 2 diabetes (Fontbonne A. The effect of metformin on the metabolic abnormalities associated with upper-body fat distribution BIGPRO Study Grope. / A. Fontbonne [et al.] // Diabetes Care. - 1996. - Vol.19. - P.920-926). The course of treatment is 12 weeks.

The practical implementation of the claimed method is illustrated by examples from clinical practice.

Example 1: patient M., 49 years old. Metabolic syndrome: stage II hypertension, risk 3; nutritional and constitutional obesity of the I degree; dyslipidemia.

At the time of admission to the City Endocrinology Center of Rostov-on-Don: body mass index - 33.0 kg / m ² , HOMA-IR insulin resistance index calculated according to the standard formula - 3.2, high density lipoprotein level - 0.56 mmol / l, triglycerides - 2.6 mmol / l. Figures of the daily average blood pressure according to the results of Holter monitoring: systolic blood pressure - 160 mm Hg, diastolic blood pressure - 100 mm Hg

The patient was treated with metabolic syndrome according to the claimed method. The patient was prescribed: antihypertensive diet - an increase in the diet of fruits and vegetables, limiting the intake of salt with food to 1.5 g per day, as well as products containing saturated fat and cholesterol; individually selected aerobic exercise in the form of fast walking for 30 minutes a day, five days a week with a heart rate of at least 145 per minute; taking Metformin 500 mg twice a day, at lunch and in the evening during meals. From the first day, a 1.5 mg dose of melaxen was included in the course of treatment once a day at night 30 minutes before bedtime for the first two weeks. Over the next ten weeks - at a dose of 3 mg once a day at night 30 minutes before bedtime. The total duration of treatment was 12 weeks.

After the treatment, a decrease in body mass index by 2.0 kg / m ^{2 was} recorded, and the HOMA-IR insulin resistance index by 2.5. At the same time, there was a decrease in the average daily numbers of blood pressure: systolic blood pressure - by 30 mm Hg, diastolic blood pressure - by 25 mm Hg; a decrease in the level of triglycerides by 0.7 mmol / L; an increase in the level of high density lipoproteins by 0.5 mmol / L.

Example 2: patient L., 36 years old. Metabolic syndrome: nutritional and constitutional obesity of the II degree; impaired carbohydrate tolerance; dyslipidemia.

At the time of the initial examination in the City Endocrinology Center of Rostov-on-Don: body mass index - 36.0 kg / m ² , insulin resistance index HOMA-IR, calculated by the standard formula - 7.7. The level of high density lipoproteins is 0.8 mmol / L, and triglycerides are 3.0 mmol / L.

The patient underwent a course of treatment according to the claimed method: antihypertensive diet - an increase in the diet of fruits and vegetables, limiting the intake of salt with food to 1.5 g per day, as well as products containing saturated fat and cholesterol; individually selected aerobic exercise in the form of free swimming for 30 minutes a day, five days a week with a heart rate of at least 150 per minute; 500 mg metformin twice a day, at lunch and in the evening during meals. From the first day, the preparation included melaxen at a dose of 2 mg once a day at night 30 minutes before bedtime for the first two weeks of the course and 3 mg once a day at night 30 minutes before bedtime for the next ten weeks . The total duration of treatment was 12 weeks.

After the treatment, the patient recorded a decrease in body mass index - by 2.4 kg / m ² , insulin resistance index HOMA-IR - by 4.0. At the same time, a decrease in the level of triglycerides by 1.1 mmol / L, an increase in the level of high density lipoproteins by 0.34 mmol / L was noted.

Using the proposed method, 52 people with metabolic syndrome, including 34 people with arterial hypertension, were treated in the City Endocrinology Center of Rostov-on-Don. In all patients, after treatment, a decrease in body mass index by 2.9-3.5 kg / m ^{2 was} recorded, and the HOMA-IR insulin resistance index by 2.48-2.58. At the same time, a decrease in the level of triglycerides by 0.5-0.9 mmol / L and an increase in the level of high density lipoproteins by 0.3-0.8 mmol / L were noted. In patients with arterial hypertension, a decrease in systolic blood pressure by 25-30 mm Hg was recorded, and diastolic blood pressure by 20-25 mm Hg.

Thus, in comparison with the prototype, the application of the claimed method of treating metabolic syndrome allowed to reduce the course of treatment by 9 months, increase the decrease in body mass index by 2.0-2.6 kg / m ² , increase the decrease in the HOMA-IR insulin resistance index by 0 , 9-1.0.

Claims (1)

A method of treating the metabolic syndrome, which provides for the appointment during the course of treatment of an antihypertensive diet, individually selected aerobic exercise and the drug metformin, characterized in that in addition to the course of treatment from the first day, they take the drug melaxen at night 30 minutes before bedtime in a dose of 1-2 mg for the first two weeks of the course, at a dose of 3 mg for the next ten weeks, metformin is prescribed 500 mg twice a day; the course of treatment is 12 weeks.