RU2677526C1 - Method of diagnostics of metabolic syndrome by ultrasonic lipometry - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: invention relates to the field of medicine, namely to diseases associated with metabolic disorders, and can be used to diagnose the metabolic syndrome. Ultrasonic method measures the maximum thickness and width of the pre-mesenteric fat. With a thickness of pre-mesenteric fat of ≥1.8 cm and/or width of pre-mesenteric fat of ≥7.0 cm metabolic syndrome is diagnosed.EFFECT: method provides accurate diagnostics due to ultrasonic lipometry.1 cl, 4 dwg, 2 tbl, 4 ex

Description

The invention relates to medicine, in particular to diseases associated with metabolic disorders, and can be used to diagnose metabolic syndrome (MS) based on ultrasonic measurement of parameters of pre-mesenteric fat.

MS was originally included in the 9th international classification of diseases as a separate disease. However, after several years in the early 90s, MS was excluded from the 10th international classifier of diseases and today it is considered as a special condition of the patient, which is not a diagnosis, but is considered as a risk factor, the outcome of which may be type 2 diabetes mellitus, severe forms of obesity, arterial hypertension, coronary heart disease. In addition, MS is dangerous not only as a risk factor for the development of the above diseases, but also as a predictor of their complications and adverse outcome.

Today, despite a common understanding of the pathogenesis of MS and the medical community accepting the totality of the primary signs of this condition (overweight, high blood pressure, dyslipidemia with increased triglycerides, decreased high density lipoprotein cholesterol, increased low density lipoprotein cholesterol, insulin resistance), accurate generally accepted There are no criteria for metabolic syndrome. Several different approaches to the “digitization and scaling” of the primary criteria for diagnosing MS are proposed: criteria formulated by the World Health Organization (WHO); principles laid down in the clustering of symptoms of MS from the International Diabetes Federation (IDF); the criteria of the American National Training Committee for the Exchange of Cholesterol - ATP III, as well as the domestic criteria of the All-Russian Scientific Society of Cardiology (GFCF).

Currently, one of the most used diagnostic criteria for detecting MS is the criteria proposed by the group of experts of the National Institute of Health USA - NCEP ATP III (Adult Treatment Panel III) [1], as well as proposed by the International Diabetes Federation IDF [2]; similar criteria are summarized in the recommendations of the All-Russian Scientific Society of Cardiology VNOK, 2010 [3].

The NCEP ATP III, 2001 classification includes the following criteria: central (abdominal) obesity - waist circumference (OT)> 102 cm (men), OT> 88 cm (women); blood triglycerides (TG) levels ≥150 mg / dl; high density lipoprotein (HDL) cholesterol <40 mg / dl (men), <50 mg / dl (women); blood pressure (BP) ≥130 / 85 mmHg; fasting plasma glucose ≥110 mg / dl. For the diagnosis of MS, 3 criteria are required.

The IDF classification, 2005 includes the main criterion: central obesity FR> 94 cm (men), FR> 80 cm (women) for Caucasoid populations; additional criteria: TG level ≥150 mg / dl (1.7 mmol / l); HDL level <40 mg / dl (1.03 mmol / L, men), <50 mg / dl (1.29 mmol / L, women); HELL ≥130 / 85 mm Hg; fasting plasma glucose ≥100 mg / dL (5.6 mmol / L) or pre-diagnosed diabetes mellitus. For the diagnosis of MS, the presence of the main criterion and any 2 additional criteria is required.

The classification of GFCF, 2010 includes the main criterion: central obesity FROM> 94 cm (men), FR> 80 cm (women); additional criteria: TG level ≥1.7 mmol / l; HDL level <1.0 mmol / L (men), <1.2 mmol / L (women); low density lipoprotein cholesterol (LDL) ≥3.0 mmol / L; HELL ≥140 / 90 mm Hg; fasting plasma glucose ≥6.1 mmol / L; plasma glucose 2 hours after and glucose tolerance test (TSH) in the range of ≥7.8 mmol / L and ≤11.1 mmol / L. For the diagnosis of MS, the presence of the main criterion and any 2 additional criteria is required.

For all groups of criteria, central obesity is the main one, plus for the diagnosis of MS, a biochemical assessment of the level of triglycerides and cholesterol of high density lipoproteins and blood glucose is necessary.

Thus, a drawback of traditional methods is the implementation of several laboratory techniques related to venipuncture and sampling of biological material, as well as the cost of reagents for laboratory analysis.

The well-known "Method for the diagnosis of metabolic syndrome", RF patent No. 2444298 (IPC A61B 10/00; A61B 8/00; A61B 5/02; A61B 5/107). This method reveals the presence of abdominal obesity, arterial hypertension, fasting hyperglycemia, hypertriglyceridemia, hypoalphacholesterolemia, hyperuricemia, non-alcoholic fatty liver disease, additionally detect overweight or obesity regardless of the type of fat deposition, insulin resistance, hypercholesterolemia. Then determine the severity of each component in points. And by the sum of the points, as well as by the presence of the necessary set of components, the metabolic syndrome, its severity and the risk of development are diagnosed.

The disadvantage of this method is its complexity, complexity, because it is necessary to conduct a lot of biochemical analyzes related to venipuncture, sampling and the study of biological material, the need for point calculation.

The well-known "Method for the diagnosis of metabolic syndrome", RF patent No. 2336807 (IPC AB 5/02), in which the diagnosis of metabolic syndrome includes the determination of the main symptom - abdominal obesity (waist circumference over 80 cm in women and 94 cm in men), as well as additional criteria: arterial hypertension (BP ≥140 / 90 mm Hg), increase triglycerides (≥1.7 mmol / L), lower cholesterol high density lipoproteins (<1.0 mmol / L in men and <1, 2 mmol / L in women), low-density lipoprotein cholesterol (> 3 mmol / L) ), fasting hyperglycemia (glucose ≥6.1 mmol / L), impaired glucose tolerance (plasma glucose 2 hours after glucose loading ≥7.8 mmol / L and ≤11.1 mmol / L), sleep apnea.

The disadvantage is the complexity due to the number of studies and high cost. So, to identify the three necessary criteria for MS, it is necessary to conduct a range of biochemical and hormonal studies, including a lipid profile, determination of insulin levels, and glucose tolerance test.

All these methods include the need for a large number of diagnostic studies according to the traditional criteria of the metabolic syndrome, which greatly complicates the diagnosis of the metabolic syndrome, affects the timing of the examination and cost.

The metabolic syndrome is characterized by an increase in the mass of visceral fat, a decrease in the sensitivity of peripheral tissues to insulin and hyperinsulinemia (GI), which cause disorders of carbohydrate, lipid, purine metabolism and arterial hypertension (AH). It should be noted that in determining the traditional criterion for diagnosing the metabolic syndrome - obesity, the type of obesity and the distribution of fat are more important than standard indicators of anthropometry. The amount of visceral fat plays a more significant role in the pathogenesis of dysmetabolic status and the development of cardiovascular diseases than the body mass index [4-6]. Visceral adipose tissue has high auto-, para- and endocrine activity, which forms biological effects for the development and progression of insulin resistance and compensatory hyperinsulinemia - the main link in the pathogenesis of metabolic syndrome in adults and children and unfavorable cardiometabolic status [4, 7, 8]. This determines the importance of using a simple and non-invasive indicator of visceral adipose tissue in order to assess the likelihood of metabolic syndrome.

Known methods for ultrasound diagnosis of adipose tissue. For example, "A method for ultrasonic diagnosis of visceral obesity" RF patent No. 2407440 (IPC AB 8/00), in which the thickness of a layer of visceral fat is examined. Before conducting an ultrasound, oral contrasting of the stomach with 200 ml of degassed liquid is performed. Calculate S (mm) according to the formula S = l-h, where l is the distance between the white line of the abdomen and the anterior wall of the aorta, and h is the distance between the walls of the stomach. At S> 30 mm, visceral obesity is diagnosed.

This method only identifies visceral obesity, which is not a mandatory statement of the presence of MS, and therefore cannot be used to diagnose MS. Also, this method is time-consuming and time-consuming, because requires additional preparation of the patient for research.

The known "Ultrasonic method for determining the thickness of adipose tissue in the abdominal region" RF patent No. 2525664, (IPC AB 8/00), which examines the thickness of visceral fat tissue to the left and right of the midline of the body (as the distance between the back surface of the rectus abdominis muscles and the anterior the wall of the abdominal aorta or the lower surface of the hooked process of the pancreatic head, with the subsequent determination of the arithmetic mean thickness of each) and the thickness of the subcutaneous adipose tissue (as the distance between the back surface of the tissue to burns and the front surface of the tissue of the rectus abdominis muscles).

This method estimates the thickness of the subcutaneous and visceral adipose tissue and increases the assessment of the information content of the amount of fat in the body, but does not determine the criteria for the metabolic syndrome and therefore is not intended for its diagnosis.

Reference methods for assessing the anatomical size of fat depots (subcutaneous, visceral) are computed tomography techniques: multilayer computed tomography (MSCT) and magnetic resonance imaging (MRI) [9-11]. However, these methods include exposure to ionizing radiation, have a high research cost and are time-consuming to complete, which hinders their use in widespread practice.

Pre-mesenteric (preperitoneal) fat (permanent) depot is a proxy indicator of visceral fat, easily accessible for ultrasound evaluation. It is located in the epigastric region between the posterior surface of the white line of the abdomen and the parietal sheet of the peritoneum (mesenterium), which is in direct contact with the front surface of the left lobe of the liver. A high degree of correlation of ultrasound measurements of permanent residence with CT and MRI data was shown in the Mongoloid population [12, 13], in adult Caucasians [10, 11] and children [14]. Including, earlier, the authors of this application validated the accuracy of ultrasonic lipometry against reference measurements of MSCT [15].

The objective of the proposed invention is to create a method that allows to simplify the diagnosis of metabolic syndrome while maintaining a high level of accuracy, eliminating laboratory research methods associated with venipuncture and sampling of biological material, which will significantly reduce the time of diagnosis and cost.

The essence of this method lies in the fact that the ultrasonic method measures the maximum thickness and width of the pre-emsenteric fat, and with the thickness of the pre-emsenteric fat ≥1.8 cm and / or the width of the pre-emsenteric fat ≥7.0 cm, the metabolic syndrome is diagnosed.

The authors developed and proposed a method for the diagnosis of metabolic syndrome by measuring pre-mesenteric fat by the ultrasonic method (ultrasonic lipometry).

The studies were conducted on a randomized family-population sample of residents of the Oktyabrsky district of Novosibirsk (163 people, men and women aged 18-64 years). Ultrasound examination of pre-mesenteric fat was performed on a Vivid 7 Exp ultrasound scanner (GE Vingmed Ultrasound A.S., Horten, Norway) equipped with a standard convex abdominal sensor (2-6 MHz) in gray scale (2D) mode. Scanning was carried out in the subjects in the supine position, along the midline of the abdomen between the xiphoid process and the navel with a sensor mounted perpendicular to the skin surface. In the cross-section (axial) section, the maximum thickness of pre-mesenteric fat (PMF1) from the inner surface of the white line of the abdomen to the front surface of the liver was measured, as well as the width of the pre-mesenteric fat (PMF2) - lateral size.

In FIG. 1 shows an anatomical diagram of the surface of the epigastric region.

In FIG. 2 presents an ultrasound image of the principles of measuring the thickness (PMZH1) and width (PMZh2) of pre-emsenteric fat.

Imaging and thickness measurements of fat depots were performed in three approaches; the average value of the measurements was taken for analysis. We used epidemiological methods for assessing cardiovascular diseases (CVD) and risk factors: including anthropometry, blood pressure, blood lipid profile (total cholesterol (OXC), triglycerides (TG), cholesterol-cholesterol, cholesterol-LDL, measuring serum glucose , an assessment of diseases and other CVD risk factors Anthropometric parameters included measuring height, weight, waist circumference (OT), hip circumference (OB), height was measured with an accuracy of 0.5 cm, weight was measured (with one layer of clothing) with an accuracy of 0.1 kg OT was measured in a standing position, lower chest, above the navel in the area of the smallest circumference of the trunk. OB was measured in their widest area at the level of the greater trochanter. Circumference was measured using a soft measuring tape with an accuracy of 0.5 cm. Also in this group of participants on the basis of IDF criteria, The diagnosis of metabolic syndrome (MS) was carried out in 2006 [2], and the criteria for the metabolic syndrome were used: central obesity, OT> 94 cm (for men), OT> 80 cm (for women); additional criteria: TG level ≥1.7 mmol / l; HDL level <1.03 mmol / L (in men), <1.29 mmol / L (in women); HELL ≥130 / 85 mm Hg; fasting plasma glucose ≥100 mg / dl or previously diagnosed diabetes mellitus. MS was established in the presence of the main criterion and 2 additional ones.

To characterize the reliability of the ultrasonic assessment of permanent residence, the reproducibility of measurements was evaluated, as a result, high reproducibility of ultrasonic measurements of permanent residence was obtained: the reproducibility coefficient of measurements according to Bland-Altman was 5% and 2.5% for the thickness and width of the pre-emsenteric fat depot in a series of repeated measurements. Quantitative values (levels) of permanent residence and permanent residence associated with the presence of MS were determined using multivariate logistic regression analysis. To verify the accuracy of identification of MS based on the calculated criteria, the ROC analysis method was used (the area under the curve was estimated; optimal combinations of sensitivity and specificity were selected for the diagnosis of MS based on the calculated criteria for permanent residence). The distribution of indicators of permanent residence in the population sample did not differ from the normal (p = 0.200; Kolmogorov-Smirnov test).

We tested 7 multivariate regression models to assess the associations of the thickness of the PMI1 with the presence of MS (for every tenth increase in the size of the PMI1 starting from 1.1 cm; the reference category was set less than the tested value). The results of multivariate regression for the thickness of the permanent residence are presented in Table 1. In the multivariate logistic regression analysis, the minimum associated with MS was the thickness of permanent residence of ≥1.6 cm, which increases the risk of having MS independently by 4.5 times (OR = 4 , 54; 95% CI. 1.32-15.60; p <0.016). The thickness of the permanent residence1 ≥1.8 cm increases the risk of MS independently of other factors by 13 times (OR = 13.02; 95% CI: 3.49-48.60; p <0.0001).

In FIG. Figure 3 shows the ROC curve of the determination of MS in terms of the size of permanent residence1.

According to ROC analysis, the area under the curve for the determination of MS according to permanent residence data was Area (SD) 0.776 (0.060), 95% CI (0.658-0.894), p <0.001. The optimal combination of sensitivity and specificity was obtained for the thickness of the permanent residence1≥1.8 cm, which discriminates MS with a sensitivity of 78% and a specificity of 74%.

Five multivariate regression models were tested to assess the associations of the width of the permanent residence with the presence of MS (for each unit of increase in the size of the permanent residence starting from 4.0 cm; the reference category was set less than the tested value). The results of multivariate regression for the width of the permanent residence2 are presented in Table 2. In the regression analysis, the width of the permanent residence2≥7.0 cm 4.5 times independently increases the risk of MS (OR = 4.51; 95% CI: 1.34-15.15; p = 0.015).

In FIG. 4 shows the ROC curve of the determination of MS by the value of permanent residence2.

According to the ROC analysis, the area under the curve for the determination of MS according to permanent residence data2 was Area (SD) 0.823 (0.059), 95% CI (0.708-0.938), p <0.001. The width of the permanent residence2≥7.0 cm discriminates MS with a sensitivity and specificity of 72% and 82%, respectively.

Example 1. Surveyed S., a man of 35 years.

The following indicators were determined for the subject: OT = 95 cm, BP = 132/80 mm Hg, TG = 1.8 mmol / L, HLVP = 1.1 mmol / L, HLLP = 3.2 mmol / L, glucose blood plasma = 6.2 mmol / L. The obtained indicators allow us to state MS according to the criteria of IDF, 2006.

Then, by measuring the pre-mesenteric fat with an ultrasonic method, the maximum thickness (PERM1) and the maximum width (PERM2) of the pre-mesenteric fat were determined. The indicators were permanent residence1 = 1.9 cm and permanent residence2 = 7.5 cm.

Conclusion: PM1 = 1.9 cm, which is more than 1.8 cm, and PM2 = 7.5 cm, which is more than 7.0 cm. The subject is successfully predicted the presence of metabolic syndrome using ultrasound lipometry.

Example 2. Surveyed A., a woman of 48 years.

OT = 85 cm, BP = 154/80 mm Hg, TG = 1.6 mmol / L, HLVP = 1.0 mmol / L, HLLP = 2.8 mmol / L, plasma glucose = 5, 0 mmol / L.

The subject has central obesity and arterial hypertension; there is no MS according to IDF criteria, 2006.

Then, by measuring the pre-mesenteric fat with an ultrasonic method, the maximum thickness (PERM1) and the maximum width (PERM2) of the pre-mesenteric fat were determined. The indicators were permanent residence1 = 1.4 cm and permanent residence2 = 5.5 cm.

Conclusion: PM1 = 1.4 cm, which is below 1.8 cm, and PM2 = 5.5 cm, which is below 7.0 cm, which confirms the absence of MS in the subject according to ultrasound lipometry.

Example 3. Surveyed L., a woman of 47 years.

OT = 90 cm, BP = 138/88 mm Hg, TG = 2.1 mmol / L, HLVP = 1.3 mmol / L, HLLP = 2.8 mmol / L, blood plasma glucose = 6.0 mmol / L.

The subject has central obesity, elevated hypertriglyceridemia and elevated blood glucose, which corresponds to MS according to IDF criteria, 2006.

Then, by measuring the pre-mesenteric fat with an ultrasonic method, the maximum thickness (PERM1) and the maximum width (PERM2) of the pre-mesenteric fat were determined. The indicators were permanent residence1 = 1.8 cm and permanent residence2 = 7.4 cm.

Conclusion: permanent residence = 1.8 cm (which is equal to the threshold criterion of 1.8 cm), and permanent residence = 7.4 cm (which is more than 7.0 cm), which, according to ultrasound lipometry, suggests the presence of MS in the subject.

Example 4. Surveyed K., a man of 60 years.

The following indicators were determined for the subject: OT = 89 cm, BP = 148/92 mm Hg, TG = 1.4 mmol / L, HLVP = 0.9 mmol / L, HLLP = 4.0 mmol / L, glucose blood plasma = 5.2 mmol / L. The patient has arterial hypertension and dyslipidemia, but there is no central obesity. The obtained indicators do not correspond to the presence of MS according to the criteria of IDF, 2006.

Then, by measuring the pre-mesenteric fat with an ultrasonic method, the maximum thickness (PERM1) and the maximum width (PERM2) of the pre-mesenteric fat were determined. The indicators were: permanent residence = 1.6 cm and permanent residence = 5.9 cm.

Conclusion: permanent residence = 1.6 cm (which is lower than 1.8 cm), and permanent residence = 5.9 cm (which is less than 7.0 cm), and thus, according to the data of ultrasound lipometry, the presence of MS in the subject is also rejected.

It should be noted that not all components of the metabolic syndrome are found simultaneously and not always explicitly. Disorders, united by the framework of the metabolic syndrome, develop gradually, and for a long time proceed without obvious clinical symptoms and often begin to form in adolescence and youth.

The claimed method for the diagnosis of metabolic syndrome by ultrasonic lipometry will allow for minimal time and material resources to diagnose the metabolic syndrome both in the clinic and when conducting screening studies of the population. This method is non-invasive, simple to execute, short-lived - takes no more than 5 minutes. The proposed method will allow to carry out preventive measures at the preclinical or early stages of metabolic disorders, which will significantly increase their effectiveness, prevent the development of the most important cardiovascular and endocrine diseases accompanying the metabolic syndrome, and develop differentiated approaches to the treatment of metabolic syndrome and related diseases.

Note:

* standardized by sex and age models;

** reference group: permanent residence <1 of each value of the test indicator;

OR - indicator of relative risk Exp (B), 95% CI - 95% confidence interval OR;

p is the confidence level.

Note:

* standardized by sex and age models;

** reference group: permanent residence <2 of each integer value of the test indicator;

OR - indicator of relative risk Exp (B), 95% CI - 95% confidence interval OR;

p is the confidence level.

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Claims (1)

A method for diagnosing a metabolic syndrome by measuring ultrasonic method of premessenteric fat, which consists in measuring the maximum thickness and width of the pre-mesenteric fat, and with a thickness of pre-mesenteric fat ≥1.8 cm and / or width of the pre-mesenteric fat ≥7.0 cm, diagnose metabolic syndrome.

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