RU2778003C1 - Method for predicting the risk of developing metabolic syndrome in young males aged 18-44 years who work at night - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to functional diagnostics, and can be used to predict the risk of developing metabolic syndrome in young males aged 18-44 years working at night. After 2 days of rest and exclusion, 24 hours before the examination of taking medications, alcoholic beverages, strong tea and coffee, blood is taken from the cubital vein at 2 o’clock, 7 o’clock and at 14 o’clock in a sitting position after 10 minutes of rest using a vacutainer and a vacutainer tube in the amount of 10 ml. Then the tube is placed on a flat surface at a temperature of 20°C to form a blood clot and centrifuged 30 minutes after the moment of blood collection for 10 minutes at 2500 rpm. A serum is obtained, 2 ml of which is placed in an empty sterile plastic tube and the level of melatonin is determined by competitive enzyme immunoassay. The obtained value is compared with the age norm obtained when determining the level of melatonin in the same conditions for males of similar age groups living in a particular area, not having chronic diseases, working in standard daytime conditions. With a decrease in melatonin levels to 91-95% of the norm, the risk of developing metabolic syndrome increases by 10%. When reduced to 61-90%, the risk of developing metabolic syndrome increases by 11-40%. With a decrease of up to 60% or less, the risk of developing metabolic syndrome increases by 41-60% or higher compared to males of the same age who do not work at night.

EFFECT: method makes it possible to predict the risk of developing metabolic syndrome in people working at night, with high sensitivity, versatility, and safety of the study by determining the level of melatonin in blood serum by competitive enzyme immunoassay.

1 cl, 4 tbl, 3 ex

Description

The invention relates to medicine, and more specifically, to functional diagnostics and can be used in outpatient and inpatient practice.

A complex of disorders characterized by the presence of abdominal obesity, arterial hypertension, dyslipidemia, and carbohydrate metabolism disorders in one patient. Metabolic syndrome is associated with an increased risk of developing many diseases, including cardiovascular disease, type 2 diabetes, and some types of cancer. To prevent the development of complications and timely correction of treatment tactics, it is important to assess the risk of developing metabolic syndrome in a timely manner. This is necessary for a more thorough search in patients at high risk.

In this regard, various methods are proposed to predict the risk of developing the metabolic syndrome, while a specific patient with his anatomical and physiological features, which can also affect the effectiveness of the therapy, falls out of sight.

There is a method for predicting the risk of developing diabetes mellitus and/or metabolic syndrome in a subject or for diagnosing metabolic syndrome in an object (patent No. 2685713, G01N 33/68, 04/23/2019).

The essence of the method: determine the level of pro-neurotensin-117 or its fragments of at least 5 amino acids or pro-neurotensin-117 containing peptides from the biological fluid obtained from the object. Elevated levels of pro-neurotensin-117 are predictive of an increased risk of diagnosing metabolic syndrome, where the subject does not have diabetes. The method is carried out according to the immunological analysis. The level of pro-neurotensin-117 above 78 pmol/l was considered elevated.

The disadvantage of this method is the diagnosis of the risk of metabolic syndrome without taking into account the individual characteristics of the patient.

A known method for predicting the metabolic syndrome in arterial hypertension in men (patent No. 2367950, G01N 33/48, 20.09.2009).

The essence of the method: in a patient with arterial hypertension, biochemical parameters are determined (CHSLPVP - high-density lipoprotein cholesterol (mmol/l), CHSLNP - low-density lipoprotein cholesterol (mmol/l), cholesterol - total cholesterol (mmol/l)), stability is calculated cell membranes (SCM (sec)). The calculation is carried out according to the formula K=7.6518-0.01886*SKM-3.11322*CHSLPVP+0.58455*CHSLPNP-0.2674*((CS-CHSLPVP)/CHSLPVP). When the value of the coefficient K≤1.2, a high risk of developing the metabolic syndrome is predicted, with a value of K≥2.5, a low probability of the metabolic syndrome is predicted in arterial hypertension in men.

The disadvantages of this method are: rank assessment of the risk of developing metabolic syndrome with assignment of the result to one of three possible classes (low, medium or high) without the possibility of quantitatively measuring the likelihood of developing this syndrome in a particular patient; the purpose of the method for detecting metabolic syndrome in general therapeutic patients; lack of indication of the timing of the formation of the metabolic syndrome in patients with different degrees of risk of its development;

A known method for assessing the risk of developing metabolic syndrome in apparently healthy individuals, including the determination of adiponectin, retinol-binding protein (RBP4) and proinsulin in biological samples of the patient; when the content of adiponectin is less than 2.8 mg/l (μg/ml), RBP4 - more than 43 mg/l, proinsulin - more than 2.2 pmol/l, a conclusion is made about the risk of developing metabolic syndrome; when the content of adiponectin is more than 2.8 mg/l (μg/ml), RBP4 is less than 43 mg/l, proinsulin is less than 2.2 pmol/l, the metabolic syndrome is unlikely (WO 2009141352 (A2) Risk analysis in patients with and without metabolic syndrome. Publication date 26.11.2009, G01N 33/68).

The disadvantage of this method is that it does not allow to determine the degree of risk and severity of the metabolic syndrome and is not effective enough for a qualitative assessment of the presence or absence of this risk. This is due to the fact that the relationship of the markers used in the method with the metabolic syndrome is not unambiguous. For example, adiponectin has a pleiotropic (multiple) effect in the body and can be a marker not only for obesity, insulin resistance, diabetes mellitus, but also for other pathological processes and diseases, such as inflammation, atherosclerosis. RBP4 is one of the markers of insulin resistance, but can also be detected in healthy individuals with a hereditary predisposition to diabetes mellitus. Thus, the method does not make it possible to distinguish between the presence of a metabolic syndrome in a patient and the risk of its development in the future. In addition, the implementation of the method is associated with technical and economic difficulties: it is used only for research purposes, kits for the determination of adiponectin, retinol-binding protein and proinsulin are imported and expensive, the implementation of the known method in practical healthcare organizations is associated with high costs, including training personnel.

A known method for diagnosing metabolic syndrome, including the measurement of blood pressure, blood pressure, OT, hip circumference (OB), body weight (kg), height (m), determination of TG, alpha-CHS in the blood, serum glucose on an empty stomach and with a carbohydrate load , albumin and creatinine in the urine; identification of the following main components of the metabolic syndrome: carbohydrate metabolism disorders (CMD) - type 2 diabetes mellitus, impaired glucose tolerance, fasting hyperglycemia according to WHO criteria (1999), obesity regardless of the type of fat deposition (body mass index> 30 kg / m ² ) and / or abdominal obesity (WC / OB ratio >0.9 in men and >0.85 in women), hypertriglyceridemia (HTG) (at the level of triglycerides in the blood ≥1.7 mM), hypoalphacholesterolemia (HACHS) (at the level of alpha- cholesterol <1.0 mM in men and <1.3 mM in women), arterial hypertension (AH) (BPs ≥140 mm Hg and BPd ≥90 mm Hg), microalbuminuria (with excretion of albumins in the urine ≥20 mcg/min or urinary albumin/creatinine ratio ≥30 mg/g); in the presence of HMO and at least two other main components, the metabolic syndrome is diagnosed (Grandy S., Brewer H., Cleeman J. et al. Definition of metabolic syndrome. Report of the National Heart, Lung, and Blood Institute / American Heart Association Conference on Scientific Issues Related to Definition Circulation - 2004. - Vol. 109. - P. 433-438).

The disadvantage of this method is that it does not allow to assess the severity and risk of metabolic syndrome. This is due, in particular, to the fact that the recognition of the presence of CMR as an obligatory component of the metabolic syndrome does not allow diagnosing the metabolic syndrome in individuals with the initial stages of insulin resistance, when carbohydrate metabolism is not disturbed due to compensatory hyperinsulinemia. At the same time, other components of the metabolic syndrome in the amount of 3 or more may already occur.

A known method for detecting MS, including the study of anthropometric and biochemical parameters of patients (Perova N.V., Metelskaya V.A., Mamedov M.N., Oganov R.G. Methods for early detection and correction of the metabolic syndrome // Prevention of diseases and health promotion - 2001. - 4 (1). - S. 18-31). According to this method, the presence of MS is diagnosed when at least one of the three combination options is detected:

- overweight, hypertension and isolated moderate hyperlipidemia;

- overweight, hypertension and combined dyslipoproteinemia;

- type 2 diabetes mellitus or impaired glucose tolerance (IGT) and abdominal obesity.

The mandatory complex of examinations for each of the patients who have early markers of MS includes monitoring of blood pressure, blood serum analysis for the level of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), a test for tolerance to glucose load and assessment of the total risk of developing coronary artery disease. At the same time, the following are accepted as the standards for early markers of the presence of MS:

1) blood pressure level >140/90 mm Hg;

2) overweight, with a Quetelet index> 25 kg / m ² and <30 kg / m ² or abdominal obesity (Quetelet index 30 kg / m ² ) with a waist circumference of 94 cm in men and 80 cm in women;

3) hypertriglyceridemia (TG 1.7 mmol/l);

4) hypo-alpha-cholesterolemia (HDL cholesterol 1.0 mmol/l in men and 1.3 mmol/l in women);

5) hyperglycemia (serum sugar level 6.1 mmol/l) or impaired glucose tolerance test. The disadvantages of the criteria for such a division is that they do not adequately reflect the ability to predict metabolic disorders.

An analysis of the existing methods for predicting the risk of developing the metabolic syndrome showed that none of them can be a prototype for the method proposed by the authors.

The objective of this invention is to determine the degree of risk (prognosis) for the development of metabolic syndrome in young males according to the WHO classification (2021) - 18-44 years old, working at night.

EFFECT: high sensitivity and versatility of the method; the safety of the study; the possibility of predicting the risk of metabolic syndrome in persons working at night.

This technical result is achieved by the fact that in young males (according to the WHO classification (2021) - 18-44 years old) working at night, after 2 days of rest and exclusion 24 hours before the examination of medication, alcoholic beverages, strong tea and coffee, from the cubital vein at 2 o'clock, 7 o'clock and at 14 o'clock in the sitting position after 10 minutes of rest, blood is taken using a vacutainer and a vacuum tube in the amount of 10 ml. Then the test tube is placed on a flat surface at a temperature of 20 ° C to form a blood clot and centrifuged 30 minutes after blood sampling for 10 minutes at 2500 rpm, serum is obtained, 2 ml of which is placed in an empty sterile plastic tube and the level of melatonin is determined by competitive enzyme immunoassay. The obtained value is compared with the age norm obtained by determining the level of melatonin under the same conditions for males of similar age groups living in a particular area, without chronic diseases, working under standard daytime conditions. With a decrease in the level of melatonin to 91-95% of the norm, the risk of developing metabolic syndrome increases by 10%; with a decrease to 61-90%, the risk of developing metabolic syndrome increases by 11-40%, and with a decrease of ≤60, the risk of developing metabolic syndrome increases by 41-60% and higher compared to males of the same age who do not work at night.

Persons working at night are affected by a number of unfavorable factors, among which desynchronosis associated with a violation of the natural rhythms of work and rest undoubtedly belongs.

There are currently no generally accepted concepts of desynchronosis. Most authors define it as a complex change in various physiological and mental functions of the body as a result of a violation of the daily rhythms of its functional systems.

There are no generally accepted methods for its diagnosis. However, in spite of everything, most studies in this area indicate that desynchronosis affects the rhythm of the production of the hormone melatonin, which in the human body is responsible for the regulation of many processes, including metabolic ones through its effect on fat metabolism and leptin synthesis.

To clarify the degree of risk of developing metabolic syndrome (MS) among young male employees (according to the WHO classification (2021) - 18-44 years old) working at night, the authors examined 105 patients (at the time of the initial examination, who had no registered signs of MS ) , mean age 36.5±1.5 years, whose work experience at night was from 5 to 10 years and more. All studies were carried out during one climatic period under standardized conditions for 4 years.

To establish the reference values of the level of melatonin (the physiological norm for young males living in a particular area) with the usual rhythm of work and rest (day work), a statistically homogeneous control group of apparently healthy people (81 people) was examined. Since it is now proven that the natural level of melatonin in the body decreases with age, the control group included patients of the same age groups as the main group. The results of studying the level of melatonin in them are presented in Table. one.

Examination of patients working at night showed a significant decrease in their melatonin level compared to the control group (Table 1) in a significant part of the examined. If we take the average level of melatonin in the control group as 100%, then the relationship between its decrease and the prevalence of MS in the main group had a correlation coefficient of 0.93 after 2 years from the start of observation/detection of a reduced level of melatonin (Table 2). Further observation of the patients from the main group for another 2 years did not reveal any new cases of developing MS in them, which made it possible to consider the obtained data on the prevalence of MS in individuals with different degrees of decrease in melatonin levels as a risk criterion for its development (Table 4). Studies have shown that a decrease in melatonin levels to 5% of the average values of the control group did not lead to an increase in the prevalence of MS compared with the results of pilot studies of the epidemiology of this condition in the Russian Federation, which showed that up to 20.6% of people aged 30-59 years old have MS, while with age (within the surveyed contingent, for example, at the age of 30-35 years there are no more than 10.2%), the number of patients increases.

table 2

The relationship between melatonin levels and the prevalence of MS

Group Melatonin level, compared with the average level of the control group, % The prevalence of MS (against the background of abdominal obesity),% Correlation coefficient,
r abs % Control group, n=81 100-95 6 7.4 0.89 Main group (primary examination), n=105 n=27 91-95 - - n=35 61-90 - - n=38 ≤60 - - Main group (re-examination, after 1 year), n=105 n=27 91-95 one 3.7 0.85 n=35 61-90 6 17.1 0.89 n=38 ≤60 eighteen 47.4 0.91 Main group (re-examination, after 2 years), n=105 n=27 91-95 3 11.1 0.91 n=35 61-90 fifteen 42.9 0.96 n=38 ≤60 24 63.2 0.98 Average value for the main group 0.93

When diagnosing metabolic syndrome (MS), the authors relied on recommendations developed on behalf of the Russian Ministry of Health and approved by the Russian Medical Society for Arterial Hypertension and the specialized commission on cardiology in 2013 (Methodological recommendations for the management of patients with metabolic syndrome). The authors studied the anthropometric and laboratory parameters characterizing the metabolic status of patients, as well as the level of blood pressure of young men (18-44 years old) working at night, included in the study, to confirm the hypothesis about the influence of the night nature of work on the formation of metabolic syndrome in people. .

In all patients with MS (developing over 2 years after the revealed reduced level of melatonin compared to the age norm), abdominal obesity was diagnosed (waist circumference more than 80 cm in women and more than 94 cm in men).

In addition, in accordance with the recommendations for the diagnosis of MS, the authors determined additional criteria for this condition (2 or more in each patient). The structure of additional criteria for MS in people with abdominal obesity against the background of MS is presented in Table 3.

In connection with the results obtained, the risks of developing the metabolic syndrome were assessed in accordance with Table 4.

Table 4

The relationship between the risks of developing MS and the level of melatonin

The degree of decrease in the level of melatonin in relation to the average norm,% Increased risk of developing MS for young men aged 18-44 years who work at night,% 91-95 to 10 61-90 11-40 ≤60 41 and up

In practice, the method for predicting the risk of developing metabolic syndrome in males working at night is carried out as follows. In young male patients (according to WHO criteria (2021) - 18-44 years old), working at night after 2 days of rest and exclusion 24 hours before the examination of medication, alcoholic beverages, strong tea and coffee, from the cubital veins at 7 am in a sitting position after 10 minutes of rest, blood is taken using a vacutainer and a vacuum tube in an amount of 10 ml. Set the tube on a flat surface at a temperature of 20°C to form a blood clot and centrifuge 30 minutes after blood sampling for 10 minutes at 2500 rpm. Serum is obtained, 2 ml of which is placed in an empty sterile plastic tube and the level of melatonin is determined by competitive enzyme immunoassay. The obtained value is compared with the age norm of men obtained by determining the level of melatonin under the same conditions for males of similar age groups living in a particular area, without chronic diseases, working under standard daytime conditions. With a decrease in the level of melatonin to 91-95% of the norm, the risk of developing metabolic syndrome increases by 10%; with a decrease to 61-90%, the risk of developing metabolic syndrome increases by 11-40% and with a decrease of ≤60, the risk of developing metabolic syndrome increases by 41-60% and higher compared with males of the same age who do not work at night.

Clinical examples

1. Patient S., 37 years old

Works as a car dealer. The nature of the work - daily employment 8 h / day. He has no chronic somatic diseases. Anthropometric data: height 182 cm. Weight 75 kg. Waist 88 cm. Laboratory data: serum melatonin level at 2.00; 7.00 and 14.00 h was 129.7 pg / ml, 18.2 pg / ml and 6.1 pg / ml, respectively (97.8%; 95.8% and 95.3% of the average norm for the control group, respectively). The examined did not complain about the increase in blood pressure in history. When examining blood pressure - 118 and 75 mm Hg. The level of triglycerides was 1.1 mmol/l, fasting blood glucose - 4.7 mmol/l, lipidogram and cholesterol levels (total) were normal.

Conclusion: there are no signs of metabolic syndrome.

Further observation (within 4 years) of the patient showed the absence of metabolic syndrome and its signs and normal (corresponding to the age norm) levels of melatonin.

2. Patient R., 39 years old

Worked as a taxi driver (only at night) for 4 years. On examination, there were no clinical signs of metabolic syndrome. Anthropometric data: height 176 cm. Weight 79 kg. Waist 86 cm. Laboratory data: serum melatonin level at 2.00; 7.00 and 14.00 h was 109.3 pg / ml, 13.9 pg / ml and 5.0 pg / ml, respectively (82.4%; 73.2% and 78.1% of the average norm for the control group, respectively). The level of triglycerides was 1.0 mmol/l, fasting blood glucose - 4.8 mmol/l, lipidogram and cholesterol levels (total) were normal.

Conclusion: there are no signs of metabolic syndrome. There is a decrease in the level of melatonin compared to the age norm.

After 1 year from the moment of the initial examination, an increase in blood pressure to 145 and 100 mm Hg was recorded during the examination. (the patient did not use medical correction). Anthropometric data: height 176 cm. Weight 81 kg. Waist 89 cm. Laboratory data: serum melatonin level at 2.00; 7.00 and 14.00 h was 108.2 pg / ml, 12.9 pg / ml and 5.0 pg / ml, respectively (82.0%; 73.1% and 78.1% of the average norm for the control group, respectively). The level of triglycerides was 1.1 mmol/l, fasting blood glucose - 4.9 mmol/l, lipid profile and cholesterol levels (total) were normal.

Conclusion: there are no signs of metabolic syndrome. The decrease in the level of melatonin compared with the age norm persists, arterial hypertension has appeared.

After 2 years, the patient notes a persistent increase in blood pressure to 150 and 100 mm Hg. Introduced medical correction. On medical correction, blood pressure figures do not exceed 125 and 90 mm Hg. Anthropometric data: height 176 cm. Weight 84 kg. Waist circumference 97 cm. Laboratory data: serum melatonin level at 2.00; 7.00 and 14.00 h was 109.3 pg / ml, 13.9 pg / ml and 4.9 pg / ml, respectively (82.4%; 73.2% and 78.0% of the average norm for the control group, respectively). The level of triglycerides was 1.9 mmol/l, fasting blood glucose - 6.2 mmol/l, cholesterol (total) 6.2 mmol/l, HDL cholesterol 0.9 mmol/l.

Conclusion: the metabolic syndrome was diagnosed.

3. Patient K., 38 years old

Worked as an ambulance driver (only at night) for 11 years. Over the past 6 years, there has been an increase in blood pressure to 170 and 100 mm Hg. On medical correction, blood pressure figures do not exceed 130 and 95 mm Hg. For the last 3 years there has been an increase in the level of glucose in the blood serum (drug correction + diet with carbohydrate restriction) - type 2 diabetes mellitus. Anthropometric data: height 179 cm. Weight 92 kg. Waist 105 cm.

Laboratory data: serum melatonin level at 2.00; 7.00 and 14.00 h was 62.3 pg / ml, 9.3 pg / ml and 2.8 pg / ml, respectively (47.0%; 48.9% and 43.8% of the average norm for the control group, respectively). The level of triglycerides was 2.4 mmol/l, fasting blood glucose - 8.2 mmol/l, cholesterol (total) 7.8 mmol/l, HDL cholesterol 0.7 mmol/l.

Conclusion: the metabolic syndrome was diagnosed.

Claims (1)

A method for predicting the risk of developing metabolic syndrome in young males aged 18-44 years working at night, which consists in the fact that after 2 days of rest and exclusion 24 hours before the examination of medication, alcoholic beverages, strong tea and coffee , from the cubital vein at 2 o'clock, 7 o'clock and at 14 o'clock in a sitting position after 10 minutes of rest, blood is taken using a vacutainer and a vacuum tube in the amount of 10 ml, then the tube is placed on a flat surface at a temperature of 20 ° C to form a blood clot and centrifuged 30 minutes after blood sampling for 10 minutes at 2500 rpm, serum is obtained, 2 ml of which is placed in an empty sterile plastic tube and the level of melatonin is determined by competitive enzyme immunoassay; the obtained value is compared with the age norm obtained by determining the level of melatonin under the same conditions for males of similar age groups living in a particular area, without chronic diseases, working under standard daytime conditions, while reducing the level of melatonin to 91- 95% of the norm, the risk of developing metabolic syndrome increases by 10%; with a decrease to 61-90%, the risk of developing metabolic syndrome increases by 11-40%, and with a decrease of up to 60% or less, the risk of developing metabolic syndrome increases by 41-60% and higher compared with males of the same age who do not work in night time.