RU2735706C1 - Method for prediction of risk of developing vascular lesions at early stages of carbohydrate metabolism disorders - Google Patents

Abstract

FIELD: medicine; endocrinology; cardiology; therapy; pathophysiology; preventive medicine.

SUBSTANCE: invention can be used for detecting and timely elimination of vascular lesions predictors at early stages of carbohydrate metabolism disorders. Method for prediction of risk of developing vascular lesions at early stages of carbohydrate metabolism disorders, including venous blood sampling, cholesterol level determination, characterized by that, additionally, the complex is used to determine deviation of anthropometric indicators (A), including body weight index (BWI), kg/m², (A₁); waist circumference, cm, (A₂), prognostically safe values A₁*<25 kg/m² and A₂*<80 cm in females, <94 cm in males, respectively, biochemical indicators (B)—plasma glucose on an empty stomach, mmol/l, (B₁); glycated hemoglobin (HbA1c), %, (B₂); an index of insulin resistance (HOMA-IR), U (B₃); total cholesterol (TC), mmol/l (B₄); low-density lipoprotein cholesterol (LDL-C), mmol/l, (B₅); triglycerides (TG), mmol/l. (B₆); high-density lipoprotein cholesterol (HDL-C), mmol/l. (B₇); low-density lipoprotein cholesterol (CS-non-HDL), mmol/l. (B₈); alpha₂-globulins, g/l. (B₉); beta₁- globulins, g/l, (B₁₀); C-reactive protein (CRP), mg/, (B₁₁), uric acid, mcmol/l, (B₁₂); creatinine (B₁₃) micromole/l, alanine amino-transferase (ALT), µkat/l, (C₁₄), aspartate aminotransferase (ACT), µkat/l, (B₁₅) account prognostically safe value—B₁*<6.1 mmol/l, B₂*<6.0 mmol/l, B₃*<2.5, B₄*<4.5 mmol/l, B₅*<2.5 mmol/l, B₆*<1.7 mmol/l, B₇*>1.0 mmol/l in males, >1.3 mmol/l in females, B₈*<3.4 mmol/l, B₉*<9.0 g/l, B₁₀*<10.6 g/l, B₁₁*<5 mg/l, B₁₂*<339 mcmole/l, B₁₃*<40 mkat/l, B₁₄*<40 mkat/l, haemostasis—average thrombocyte volume, fl (H₁), intensity of ADP- and collagen-induced thrombocyte aggregation, % (H₂ and H₃), aPTT, c (H₄), fibrinogen, g/l, (H₅), VII factor activity, %. (H₆), antithrombin III, %, (H₇), plasminogen %, (H₈), endothelin pmol/l, (H_9),allow for prognostic safe values—H₁*<10 fl, H₂*<64 %, H₃*<60 %, H₄*>23 c, H₅*<4 g/l, H₆*<110 %, H₇*>70 %, H₈*>80 %, H₉*<0.16 pmole/l respectively, then the difference between patient's values and prognostically safe values is determined (A₁−A₁*), (A₂−A₂*); (B₁−B₁*), (B₂−B₂*), (B₃−B₃*), (B₄−B₄*), (B₅−B₅*), (B₆−B₆*), (B₇−B₇*), (B₈−B₈*), (B₉−B₉*), (B₁₀−B₁₀*), (B₁₁−B₁₁*), (B₁₂−B₁₂*), (B₁₃−B₁₃*), (B₁₄−B₁₄*); (H₁−H₁*), (H₂−H₂*), (H₃−H₃*), (H₄−H₄*), (H₅−H₅*), (H₆−H₆*), (H₇−H₇*), (H₈−H₈*), (H₉−H₉*) respectively, and if a positive value of each of An−An*, Bn−Bn*, Hn−Hn* is 1 point, with zero or negative value of 0 points, total score (K) is determined as the sum of all the points, and if the positive sum is stated, the risk of developing vascular lesions is determined, and if the total score is zero, the risk is determined.

EFFECT: invention provides early detection and timely correction of anthropometric, biochemical and hemostasis disorders.

1 cl, 13 tbl, 2 ex

Description

The proposed invention relates to medicine, endocrinology, cardiology, therapy, pathophysiology, preventive medicine and can be used to identify and timely eliminate predictors of vascular lesions in the early stages of carbohydrate metabolism disorders (ICD).

Diabetes mellitus (DM) is a serious medical and social problem. According to IDF, by 2017, 425 million patients with diabetes were registered in the world, it is assumed that another 352 million people have impaired glucose tolerance [1]. Meanwhile, the number of inhabitants of the planet with carbohydrate metabolism disorders continues to grow and, according to the forecast, by 2045 will exceed one billion people.

Along with globalization, the features of the emergence and development of DM make a significant contribution to the significance of the problem. A wide range of biochemical changes in the absence of clinical symptoms makes the diagnosis and motivation of the patient for treatment difficult in order to prevent disabling consequences. Debuting as a metabolic disease, diabetes is accompanied by morphological and functional changes in the vascular wall, damage to target organs with the development of life-threatening conditions, cardiovascular disasters [2]. Aggressiveness and universal character of vascular lesions of various calibers determines the prognostic danger of diabetes. Currently, diabetes is recognized as one of the leading risk factors for cardiovascular disease. The likelihood of developing blindness, uremia, gangrene of the extremities in patients with diabetes is 25, 17 and 20 times higher than in the population [3]. With a high prevalence of microangiopathies, predictors of death in patients with diabetes are macrovascular lesions [4]. The risk of coronary events in patients with diabetes mellitus is comparable to the risk of patients with an established diagnosis of ischemic heart disease, and mortality from cerebrovascular disorders is 2-3 times higher than in the general population [5].

Reducing the risk of cardiovascular complications is a cornerstone of diabetology. For decades, the solution to this problem was associated with the normalization of carbohydrate metabolism indicators. However, an unexpected result of large-scale clinical studies ADVANCE (2008), ACCORD (2009) was the absence of a significant reduction in macrovascular complications against the background of strict glycemic control. The data obtained initiated a revision of a number of provisions of the theory of glucosecentricity and demonstrated the insufficient effectiveness of treatment tactics in the presence of complications. Currently, there is a need to develop a new strategy to prevent cardiovascular disorders by eliminating the leading risk factors in the early stages of the formation of pathogenetic mechanisms.

Analogs - methods are known for predicting the total risk of vascular diseases and their complications in the general population based on changes in the lipid spectrum (determination of the lipid profile using an automatic biochemical analyzer ADVIA 1650 (Bayer) [Operation Manual. USA, 2008]), with subsequent calculation risk according to nationally specific scales (risk meters) - PROCAM (Germany), ASSIGN (Sweden), Framingham (USA), Q-RICK (UK), CUORE (Italy) and others [6].

In particular, the main stages of the method include:

1. Blood sampling from a vein into a vakueta in the amount of 5 ml.

2. Placing the sample in the analyzer for 10 minutes.

3. Analysis of the results obtained. An increase in the concentration of total cholesterol and / or low density lipoproteins in combination with arterial hypertension indicates the presence of a moderate, high, or extremely high risk of developing atherosclerotic lesions.

Disadvantages of the method:

Изолированное определение показателей липидного спектра и недоучет комплекса антропометрических, биохимических и гемостазиологических изменений, участвующих в формировании сосудистых осложнений на ранних стадиях НУО, что определяет недостаточно высокую достоверность способа.

Isolated determination of lipid spectrum indices and underestimation of the complex of anthropometric, biochemical and hemostasiological changes involved in the formation of vascular complications in the early stages of CVD, which determines the insufficiently high reliability of the method.

Использование вышеперечисленных шкал, в том числе, разработанных для больных сахарным диабетом не рекомендуется [7]

The use of the above scales, including those developed for patients with diabetes mellitus, is not recommended [7]

The closest analogue is the international scale SCORE [8]

In particular, the main stages of the method include:

1. Assessment of gender and age characteristics;

2. Accounting for smoking;

3. Blood pressure levels;

4. Blood sampling from a vein into a vakueta in the amount of 5 ml;

5. Placing the sample in the analyzer for 10 minutes;

6. Analysis of the results obtained. The aggregate data - an increase in the concentration of total cholesterol, blood pressure, smoking, determine the degree of risk of death from cardiovascular complications (coronary events, myocardial infarction, aneurysm of the abdominal aorta) in different gender-age groups.

Disadvantages of the method:

Шкала разработана для оценки риска смерти от сердечно-сосудистых заболеваний и не прогнозирует риск развития сосудистых осложнений.

The scale is designed to assess the risk of death from cardiovascular disease and does not predict the risk of developing vascular complications.

Использование только основных факторов риска и недоучет комплекса антропометрических, биохимических и гемостазиологических изменений, также участвующих в формировании сосудистых осложнений на ранних стадиях НУО, что делает способ недостаточно высоко достоверным.

Using only the main risk factors and underestimating the complex of anthropometric, biochemical and hemostasiological changes, also involved in the formation of vascular complications in the early stages of CMD, which makes the method not highly reliable.

Использование шкалы SCORE для больных сахарным диабетом не рекомендуется [7].

The use of the SCORE scale for diabetic patients is not recommended [7].

Objectives of the alleged invention: early detection of a complex of predictors of vascular complications for predicting and timely elimination of the risk of angiopathies, increasing the reliability of the method.

In this regard, the complex of anthropometric (body mass index (BMI), waist circumference), biochemical (subclinical inflammation, atherogenic type of dyslipidemia, dysproteinemia, changes in purine metabolism) and hemostasiological (changes in platelet and plasma hemostasis) predictors of athero- thrombus formation in the early stages of carbohydrate metabolism disorders (GCM) - newly diagnosed type 2 diabetes mellitus (VDSD 2) and prediabetes (impaired glucose tolerance (IGT) and impaired fasting glycemia (FGN)).

The essence of the invention is that, in addition, the complex determines the deviation of anthropometric indicators (A), including - body mass index (BMI), kg / m ² (A ₁ ); waist circumference, cm (A ₂ ) take into account prognostically safe values (A ₁ * and A ₂ *, respectively) [9], biochemical parameters (B) - fasting plasma glucose, mmol / l (B ₁ ); glycated hemoglobin (HbA1c),%, (В ₂ ); insulin resistance index (HOMA-IR), units (B ₃ ); total cholesterol (TC), mmol / l (B ₄ ); low density lipoprotein cholesterol (LDL-C) mmol / l (B ₅ ); triglycerides (TG), mmol / l (B ₆ ); high density lipoprotein cholesterol (HDL-C), mmol / l (B ₇ ); low-density lipoprotein cholesterol (cholesterol-non-HDL), mmol / l (B ₈ ); alpha ₂ -globulins, g / l (B ₉ ); beta globulins, g / l (B ₁₀ ); C-reactive protein (CRP), mg / L (B ₁₁ ), uric acid, μmol / L (B ₁₂ ); alanine aminotransferase (ALT), μkat / L (B ₁₃ ), aspartate aminotransferase (ACT), μkat / L (B ₁₄ ) take into account prognostically safe values - B ₁ *, B ₂ *, B ₃ *, B ₄ *, B ₅ *, B ₆ *, B ₇ *, B ₈ *, B ₉ *, B ₁₀ *, B ₁₁ *, B ₁₂ *, B ₁₃ *, B _14, *, respectively [9, 10], hemostasiological parameters (H) - average platelet volume (SOT), fl (H ₁ ), intensity of ADP- and collagen-induced platelet aggregation,% (H ₂ and H ₃ ), activated partial thromboplastin time (AhTT), s (H ₄ ), fibrinogen, g / l (H ₅ ), activity of factor VII,% (H ₆ ), antithrombin III,% (H ₇ ), plasminogen%, (H ₈ ), endothelin, pmol / l (H ₉ ) take into account prognostically safe values - H ₁ *, H ₂ *, H ₃ *, H ₄ *, H ₅ *, H ₆ *, H ₇ *, H ₈ *, H ₉ *, respectively [10]. Next, the difference (ΔA, ΔB, ΔH) is determined between the patient's indicators and the prognostically safe values of the corresponding indicators:

Δ A = (A ₁ - A ₁ *) + (A ₂ - A ₂ *);

Δ B = (B ₁ - B ₁ *) + (B ₂ - B ₂ *) + (B ₃ - B ₃ *) + (B ₄ - B ₄ *) + (B ₅ - B ₅ *) + (B ₆ - V ₆ *) + (V ₇ - V ₇ *) + (V ₈ - V ₈ *) + (V ₉ - V ₉ *) + (V ₁₀ - V ₁₀ *) + (V ₁₁ - V ₁₁ * ) + (B ₁₂ - B ₁₂ *) + (B ₁₃ - B ₁₃ *) + (B ₁₄ - B ₁₄ *);

Δ H = (H ₁ - H ₁ *) + (H ₂ - H ₂ *) + (H ₃ - H ₃ *) + (H ₄ - H ₄ *) + (H ₅ - H ₅ *) + (H ₆ - H ₆ *) + (H ₇ - H ₇ *) + (H ₈ - H ₈ *) + (H ₉ - H ₉ *)

and determine the total number of points (K) by the formula:

K = Δ A + Δ B + Δ H

if the amount is positive, the risk of developing angiopathies is determined, if negative - its absence.

EFFECT: due to early detection and timely correction of anthropometric, biochemical and hemostasiological disorders, they create the possibility of reducing the frequency and intensity of development of diabetic vascular complications, contribute to an increase in the effectiveness of preventive measures aimed at reducing the number of cases of transition of prediabetes to type 2 diabetes mellitus, - the possibility of achieving remission of the disease. The inclusion of additional indicators (anthropometric, biochemical, hemostasiological) in the diagnostic range increases the reliability of the method.

Implementation of the method:

The study of anthropometric indicators - height, weight, waist circumference is measured in underwear and without shoes. Waist circumference is measured with a centimeter tape at the middle of the distance between the lower rib and the iliac crest and is expressed in centimeters (cm), body mass index (BMI) is calculated as weight divided by the square of height in meters (kg / m ² ), a study of biochemical and hemostasiological indicators are carried out by standard clinical and biochemical methods: hemogram - ADVIA 120 analyzer; fasting plasma glucose, TC, LDL-C, HDL-C, HDL-C, TG, Apo-B, CRP, creatinine, bilirubin, ALT, ACT, urea biochemical analyzer ADVIA 1650; HbA1c on a D-10 HPLC analyzer (Bio-Rad Laboratiries, USA), electrophoresis of protein fractions in agarose gel (Hydrasys, Sebia, France). C-peptide, insulin with an automatic immunochemical analyzer ADVIA Centaur (Siemens, Germany), biochemical coagulogram with an automatic analyzer ACL TOP 700 (Instrumentation Laboratory Company, USA) using the manufacturer's reagents, fibrinogen - by a coagulation method, endothelium-1-38 using ELISA, activity VII factor analyzer of hemostasis STArt-4 (Diagnostica Stago, France), the activity of plasminogen and antithrombin-III by turbidimetric and chromogenic methods. Platelet aggregation activity (AACP) by an analyzer of platelet aggregation properties (Solar AP-2110, Belarus) using adenosine diphosphate (ADP) aggregation inducer 1.25 μg / ml and 2.5 μg / ml and collagen as an inducer. The glomerular filtration rate GFR (ml / min / 1.73 m ² ) is determined by the calculation method according to the CKD-EPI formula:

141 × min × [min plasma creatinine (mg / dl) / kappa or 1) ^alpha * × [max plasma creatinine (mg / dl) / kappa or 1) ^-1.209 × 0.993 ^Age × 1.018 (for women) × 1.159 (for representatives of the black race), where kappa 0.7 for women and 0.9 for men, alpha - (-0.329 for women) and (-0.411 for men).

The method was tested on a contingent of 64 volunteers aged 40-65 years, initially considering themselves healthy and not receiving any drug therapy, in whom, according to the screening data, early disorders of carbohydrate metabolism - prediabetes were identified and then confirmed by performing an oral glucose tolerance test (OGTT) and VDSD type 2. The control group consisted of healthy non-smokers without signs of metabolic abnormal phenotype and not taking any drugs.

The groups were comparable in terms of sex and age, however, patients with early CMR were overweight and / or obese and, accordingly, body mass index (BMI) and waist circumference (WC) were 1.4 times higher than the control values (p <0.001) (Table 1).

Analysis of biochemical parameters along with hyperglycemia, hyperinsulinemia and the presence of insulin resistance (IR) revealed a wide range of metabolic changes in the early stages of ICR (Table 2).

The revealed biochemical changes are mostly associated with anthropometric indicators of the metabolic abnormal phenotype, as well as with markers of hyperinsulinemia and insulin resistance (IR). In particular, the relationships of average strength between RT and the concentration of C-peptide, insulin, insulin resistance index HOMA-IR, C-reactive protein, triglycerides, HDL-C (-), uric acid, ALT were determined (Table 3).

CRP, TG, very low density lipoprotein cholesterol (VLDL-C), HDL-C (-), uric acid, transaminases are closely related to hyperinsulinemia and IR. The level of fasting glycemia correlates with waist circumference, HOMA-IR (r = 0.40, p <0.001), concentration of C-peptide (r = 0.32, p = 0.01) and Apo B. In addition, according to the correlation analysis revealed the presence of multiple direct links of moderate strength between C-reactive protein and OT, BMI, as well as insulin levels, HOMA-IR, fasting hyperglycemia, HbA1c, TC, LDL-C, TG, Apo B, uric acid, ALT.

Metabolic changes, subclinical inflammation are able to play the role of a trigger in the occurrence of endothelial dysfunction, and subsequently be a link in the development of pathological processes that contribute to athero formation and an increase in thrombogenic potential. In order to identify significant metabolic factors contributing to hemostasiological changes in the early stages of ICR, the key markers for assessing the state of the vascular, platelet and plasma components of the hemostatic system were studied.

It was found that patients with early CMD have a twofold increase in endothelin concentration (Table 4), which is accompanied by the presence of direct links between the endothelin concentration and the OT / V ratio (r = 0.27, p = 0.03), the level of glycemia (coefficients correlations in pairs HbA1c - endothelium and fasting glucose - endothelium were, respectively, r = 0.46, p <0.001 and r = 0.28, p = 0.03), CRP (r = 0.32, p = 0.01) , as well as alpha ₁ -globulins (r = 0.26, p = 0.04), PTT (r = 0.27, p = 0.04), collagen-induced platelet aggregation (r = -0.30, p = 0.03).

Endothelial dysfunction is an independent cause of changes in the activity of platelets (CP), however, the revealed variety of biochemical changes in the early stages of CMD can also have an additive effect on various levels of platelet hemostasis. The analysis of the number of CPs and their sizes carried out in this regard revealed an increase in the mean volume of platelets (MOT), inversely associated with an increase in the concentration of LDL cholesterol (r = -0.30, p = 0.02) and CRP (r = -0.26, p = 0.04). No significant quantitative changes in CP in patients with early stages of CMD were found, however, according to the data of correlation analysis, there are direct links between the number of CPs with inflammation markers - the concentration of CRP (r = 0.27, p = 0.03) and FG (r = 0.34 , p = 0.01), which may indicate the effects of acute phase proteins on the processes of thrombocytopoiesis.

In the parameters of aggregation activity, an increase in ADP- and collagen-induced aggregation was noted by 20% and 9%, respectively. The revealed connections between ADP-induced aggregation with the OT / OT ratio (r = -0.28, p = 0.02), uric acid level (r = -0.25, p = 0.048), transaminases (ACT (r = -0 , 31, p = 0.01, ALT r = -0.34, p = 0.01) were predominantly inverse.In addition, the correlation analysis made it possible to establish other significant relationships that complement the picture of endothelial dysfunction, its relationship with AACP and In particular, low-intensity feedbacks were revealed between collagen-induced aggregation and the concentration of endothelin, CRP, triglycerides, fasting plasma glucose, HbA1c and insulin resistance index, confirming the variety of metabolic influences on the endothelium.

Strengthening the functional activity of CP is traditionally considered as an initiating factor for activating the internal coagulation pathway. Meanwhile, in patients with early stages of CMD, a wide range of metabolic changes were revealed, each of which is capable of influencing various components of the coagulation, anticoagulation, and fibrinolytic system. In this regard, the main indicators and correlation links have been analyzed both directly between the components of the hemostasis system and with altered metabolic indicators.

Assessment of the state of the coagulation unit revealed signs of its activation in the early stages of ICR, which was manifested by an increase in the activity of factor VII, fibrinogen, as well as a shortening of PTT and, accordingly, MHO (see Table 4).

At the same time, direct links were established between the activity of factor VII and AT III (r = 0.43, p <0.001), plasminogen (r = 0.32, p = 0.01), as well as reverse links with PTI (r = -0, 36, p = 0.04) and MHO (r = -0.40, p = 0.02). Significant changes in the indices of the internal pathway of coagulation in the early stages of ICR were not found, however, according to the data of correlation analysis, inverse mathematical, but direct functional relationships between the APTT and the concentration of glucose, peroxides and direct with PTT were revealed. In terms of the plasma component, a decrease in AT III activity was noted positively associated with the concentration of TC (r = 0.25, p = 0.04), HDL-C (r = 0.30, p = 0.02), Apo-A (r = 0.25, p <0.05), bilirubin (r = 0.28, p = 0.02), and factor VII (r = 0.43 p <0.001), while the level of plasminogen in patients with CMD was increased and showed direct links with the activity of factor VII (r = 0.32, p = 0.01), fibrinogen concentration (r = 0.25, p <0.04) and inverse with MHO (r = -0.33, p = 0.01).

Thus, the results obtained indicate the presence of diverse changes in metabolic parameters at the early stages of ICR, involving the key indicators of carbohydrate, protein, lipid, purine metabolism and hemostasis with the development of hyperglycemia, atherogenic dyslipidemia, an increase in the concentration of lactic acid, fibrinogen, endothelial dysfunction and prothrombogenic readiness with activation of vascular-platelet, coagulation, decrease in anticoagulant and fibrinolytic potential. The revealed changes are closely related to the anthropometric parameters of the metabolically abnormal phenotype, as well as to laboratory markers of hyperinsulinemia, insulin resistance, and subclinical inflammation.

Examples of

Example 1. Patient D, 54 years old. At the time of examination, he considers himself a healthy person, does not make any complaints. He does not smoke, is obese 1 tbsp, blood pressure 135/85 mm. rt. Art. Changes were revealed in anthropometric and laboratory parameters (Table 6). When carrying out a glucose-tolerant test - fasting plasma glucose - 6.6 mmol / l, after 2 hours - 7.6 mmol / l. According to instrumental methods (ECG, ECHO-CS, ophthalmoscopy), laboratory markers of renal functions (GFR - 100 ml / min / 1.73 m ² , daily albumin loss - 0.8 mg / 24 hours albumin-creatinine ratio <3 mg / mmol ) no signs of vascular lesions were found.

The diagnosis was made: Alimentary-constitutional obesity of the 1st degree (BMI 34 kg / m ² ). Impaired fasting glucose.

Calculated vascular risk:

Δ A = (A ₁ - A ₁ *) + (A ₂ - A ₂ *) = (+1 point) + (+1 point) = + 2 points

Δ B = (B ₁ - B ₁ *) + (B ₂ - B ₂ *) + (B ₃ - B ₃ *) + (B ₄ - B ₄ *) + (B ₅ - B ₅ *) + (B ₆ - V ₆ *) + (V ₇ - V ₇ *) + (V ₈ - V ₈ *) + (V ₉ - V ₉ *) + (V ₁₀ - V ₁₀ *) + (V ₁₁ - V ₁₁ * ) + (B ₁₂ - B ₁₂ *) + (B ₁₃ - B ₁₃ *) + (B ₁₄ - B ₁₄ *) = (+1 point) + (+1 point) + (+1 point) + (+1 point) + (+1 point) + (+1 point) + (+1 point) + (+1 point) + (0 point) + (+1 point) + (0 point) + (+1 point) + ( +1 point) + (0 point) = +11 points

Δ H = (H ₁ - H ₁ *) + (H ₂ - H ₂ *) + (H ₃ - H ₃ *) + (H ₄ - H ₄ *) + (H ₅ - H ₅ *) + (H ₆ - H ₆ *) + (H ₇ - H ₇ *) + (H ₈ - H ₈ *) + (H ₉ - H ₉ *) = (0 point) + (+1 point) + (+1 point) + (+1 point) + (0 points) + (+1 point) + (0 points) + (0 points) + (+1 point) = +5 points.

Estimated risk of vascular lesions at baseline

Δ А + Δ В + Δ Н = (+2) + (+11) + (+5) = +18

revealed a positive vector, indicating the risk of vascular lesions.

Patient D. recommendations on lifestyle modifications - dissent body weight (reducing and maintaining BMI in the range 20-25 kg / m ^2, the waist circumference less than 102 cm by aerobic physical load (FN) as portability (moderate aerobic FN of at least 150 minutes per week (30 days a week) or intense aerobic exercise capacity of at least 75 minutes per week (15 minutes 5 days a week) or an equivalent combination, reduced calorie intake with restriction of digestible carbohydrates, low consumption of saturated fat and emphasis on whole grains , vegetables, fruits and fish The need for drug therapy is explained - overcoming and eliminating insulin resistance (metformin 1700 mg / day), lipid-lowering therapy (rosuvastatin 20 mg / day), with dose adjustment according to lipid spectrum indicators.

The patient partially complied with the recommendations. Six months later, according to instrumental methods (ECG, ECHO-CS, ophthalmoscopy), laboratory markers of renal functions (GFR - 102 ml / min / 1.73 m ² , albu-min-creatinine ratio <3 mg / mmol), signs of vascular lesions not found. Blood pressure is 135/89 mm. rt. Art. In anthropometric and laboratory parameters, changes were revealed (Table 7).

The calculation of the risk of developing angiopathies was performed:

Δ A = (A ₁ - A ₁ *) + (A ₂ - A ₂ *) = (+1 point) + (+1 point) = +2 points

Δ B = (B ₁ - B ₁ *) + (B ₂ - B ₂ *) + (B ₃ - B ₃ *) + (B ₄ - B ₄ *) + (B ₅ - B ₅ *) + (B ₆ - V ₆ *) + (V ₇ - V ₇ *) + (V ₈ - V ₈ *) + (V ₉ - V ₉ *) + (V ₁₀ - V ₁₀ *) + (V ₁₁ - V ₁₁ * ) + (B ₁₂ - B ₁₂ *) + (B ₁₃ - B ₁₃ *) + (B ₁₄ - B ₁₄ *) = (+1 point) + (+1 point) + (+1 point) + (+1 point) + (+1 point) + (+1 point) + (+1 point) + (+1 point) + (1 point) + (+1 point) + (+0 point) + (+1 point) + (+1 point) + (0 points) = +12 points

Δ H = (H ₁ - H ₁ *) + (H ₂ - H ₂ *) + (H ₃ - H ₃ *) + (H ₄ - H ₄ *) + (H ₅ - H ₅ *) + (H ₆ - H ₆ *) + (H ₇ - H ₇ *) + (H ₈ - H ₈ *) + (H ₉ - H ₉ *) = (0 points) + (+1 point) + (+1 point) + (+1 point) + (0 points) + (+1 point) + (0 points) + (0 points) + (+1 point) = +5 points.

Estimated risk of vascular lesions after 6 months:

Δ A + Δ B + Δ H = (+2) + (+12) + (+5) = +19

revealed a positive vector, with an increase in the estimated amount by 1 point compared to the baseline, which indicates an increase in the risk of developing vascular complications.

Patient D., re-informed about the high risk of developing vascular complications and the need to change the lifestyle - weight loss through aerobic physical activity (exercise in the gym daily for tolerance, but not less than 60 minutes), caloric intake (~ 1300 kcal / s restriction of easily digestible carbohydrates), table salt up to 5 g / s. Drug therapy is strongly recommended - metformin 1700 mg / day, rosuvastatin 20 mg / day, with dose adjustment according to lipid spectrum indicators, blood pressure control with Holter monitoring, followed by consideration of the advisability of prescribing drug antihypertensive therapy.

Year - the patient does not fulfill the recommendations, according to instrumental techniques (ECG, ECHO-CC ophthalmoscopy), laboratory markers of renal function (glomerular filtration rate - 96 mL / min / 1.73 m ² daily loss Albumin - 12 mg / 24 hours, albumin creatinine ratio <3 mg / mmol), blood pressure 150/90 mm. rt. Art. No signs of vascular lesions were found, negative dynamics of anthropometric and laboratory parameters was noted (Table 8). Diagnosis: Alimentary-constitutional obesity of the 1st degree (BMI 34 kg / m ² ). Impaired fasting glucose. Hypertension 1 degree, 1 stage, high risk.

The calculation of the risk of developing angiopathies was performed:

Δ A = (A ₁ - A ₁ *) + (A ₂ - A ₂ *) = (+1 point) + (+1 point) = +2 points

Δ B = (B ₁ - B ₁ *) + (B ₂ - B ₂ *) + (B ₃ - B ₃ *) + (B ₄ - B ₄ *) + (B ₅ - B ₅ *) + (B ₆ - V ₆ *) + (V ₇ - V ₇ *) + (V ₈ - V ₈ *) + (V ₉ - V ₉ *) + (V ₁₀ - V ₁₀ *) + (V ₁₁ - V ₁₁ * ) + (B ₁₂ - B ₁₂ *) + (B ₁₃ - B ₁₃ *) + (B ₁₄ - B ₁₄ *) = (+1 point) + (+1 point) + (+1 point) + (+1 point) + (+1 point) + (+1 point) + (+1 point) + (+1 point) + (0 point) + (+1 point) + (+1 point) + (+1 point) + (+1 point) + (0 points) = +13 points

Δ H = (H ₁ - H ₁ *) + (H ₂ - H ₂ *) + (H ₃ - H ₃ *) + (H ₄ - H ₄ *) + (H ₅ - H ₅ *) + (H ₆ - H ₆ *) + (H ₇ - H ₇ *) + (H ₈ - H ₈ *) + (H ₉ - H ₉ *) = (0 points) + (+1 point) + (+1 point) + (+1 point) + (1 point) + (+1 point) + (0 points) + (0 points) + (+1 point) = +6 points.

Estimated risk of vascular lesions after one year:

Δ A + Δ B + Δ H = (+2) + (+12) + (+6) = +20

revealed a positive vector, with an increase in the calculated amount by 1 point compared to the baseline, which indicates the progression of metabolic changes and the aggravation of the risk of developing vascular complications.

Patient D., re-informed about the high risk of developing vascular complications and the need to change the lifestyle - weight loss through aerobic physical activity (exercise in the gym daily for tolerance, but not less than 60 minutes), caloric intake (-1300 kcal / s restriction of easily digestible carbohydrates), the need to use drug therapy - metformin 1700 mg / day, hypolipidemic therapy (rosuvastatin 20 mg / day) with dose adjustment according to the lipid spectrum, antihypertensive therapy (enalapril maleate 2.5 mg / s) with correction for arterial pressure,

Four years later, the patient does not systematically follow the recommendations, negative dynamics of anthropometric and laboratory parameters was noted (Table 9) with the transformation of prediabetes into type 2 diabetes mellitus and the presence of microvascular changes in the fundus (diabetic retinal angioretinopathy OU), the appearance of microalbuminuria in urine (GFR - 75 ml / min / 1.73 m ² , albumin - 54 mg / 24 hours, albumin-creatinine ratio - 3.4 mg / mmol). Blood pressure 170/100 mm. rt. Art. ECG shows signs of left ventricular hypertrophy.

Diagnosis: Type 2 diabetes mellitus for the first time. Diabetic retinal angioretinopathy - OU, Diabetic nephropathy grade 1 CKD C2, A2. Alimentary-constitutional obesity of the 2nd degree. Hypertension grade 2, stage II, risk 4.

The calculation of the risk of developing angiopathies was performed:

Δ A = (A ₁ - A ₁ *) + (A ₂ - A ₂ *) = (+1 point) + (+1 point) = +2 points

Δ B = (B ₁ - B ₁ *) + (B ₂ - B ₂ *) + (B ₃ - B ₃ *) + (B ₄ - B ₄ *) + (B ₅ - B ₅ *) + (B ₆ - V ₆ *) + (V ₇ - V ₇ *) + (V ₈ - V ₈ *) + (V ₉ - V ₉ *) + (V ₁₀ - V ₁₀ *) + (V ₁₁ - V ₁₁ * ) + (B ₁₂ - B ₁₂ *) + (B ₁₃ - B ₁₃ *) + (B ₁₄ - B ₁₄ *) = (+1 point) + (+1 point) + (+1 point) + (+1 point) + (+1 point) + (+1 point) + (+1 point) + (+1 point) + (1 point) + (+1 point) + (+1 point) + (+1 point) + (+1 point) + (0 points) = +13 points

Δ H = (H ₁ - H ₁ *) + (H ₂ - H ₂ *) + (H ₃ - H ₃ *) + (H ₄ - H ₄ *) + (H ₅ - H ₅ *) + (H ₆ - H ₆ *) + (H ₇ - H ₇ *) + (H ₈ - H ₈ *) + (H ₉ - H ₉ *) = (0 points) + (+1 point) + (+1 point) + (+1 point) + (1 point) + (+1 point) + (0 points) + (0 points) + (+1 point) = +6 points.

Estimated risk of vascular lesions after four years:

Δ А + Δ В + Δ Н = (+2) + (+13) + (+6) = +21

revealed a positive vector, with an increase in the estimated amount by 1 point compared to the baseline, which indicates an increase in the risk of developing vascular complications.

Thus, the failure of patient D to take measures to normalize anthropometric, biochemical and hemostasiological parameters within four years contributed to the transformation of prediabetes into type 2 diabetes mellitus with the appearance of vascular complications and a high risk of their further progression.

Example 2,

Patient Y., 57 years old.

Diagnosis: Diabetes mellitus type 2, first diagnosed. Alimentary-constitutional obesity 1 tbsp. (BMI 32 kg / m ² ).

According to instrumental methods (ECG, ECHO-CS, ophthalmoscopy), laboratory markers of renal functions (GFR - 84 ml / min / 1.73 m ² , daily albumin loss - 0.6 mg / 24 hours, albumin-creatinine ratio <3 mg / mmol), no signs of vascular lesions were found. Blood pressure is 140/90 mm. rt. Art. In laboratory parameters, in addition to insulin resistance and hyperglycemia, an excess of prognostically safe values of anthropometric, biochemical and hemostasiological parameters was revealed (Table 10).

The calculation of the risk of developing angiopathies was performed:

Δ A = (A ₁ - A ₁ *) + (A ₂ - A ₂ *) = (+1 point) + (+1 point) = +2 points

Δ B = (B ₁ - B ₁ *) + (B ₂ - B ₂ *) + (B ₃ - B ₃ *) + (B ₄ - B ₄ *) + (B ₅ - B ₅ *) + (B ₆ - V ₆ *) + (V ₇ - V ₇ *) + (V ₈ - V ₈ *) + (V ₉ - V ₉ *) + (V ₁₀ - V ₁₀ *) + (V ₁₁ - V ₁₁ * ) + (B ₁₂ - B ₁₂ *) + (B ₁₃ - B ₁₃ *) + (B ₁₄ - B ₁₄ *) = (+1 point) + (+1 point) + (+1 point) + (+1 point) + (+1 point) + (+1 point) + (0 point) + (+1 point) + (+1 point) + (+ 1 point) + (+1 point) + (+1 point) + (0 points) + (0 points) = +11 points

Δ H = (H ₁ - H ₁ *) + (H ₂ - H ₂ *) + (H ₃ - H ₃ *) + (H ₄ - H ₄ *) + (H ₅ - H ₅ *) + (H ₆ - H ₆ *) + (H ₇ - H ₇ *) + (H ₈ - H ₈ *) + (H ₉ - H ₉ *) = (0 points) + (+1 point) + (+1 point) + (0 points) + (0 points) + (+1 point) + (0 points) + (0 points) + (+1 point) = +4 points.

Estimated risk of vascular lesions at baseline

Δ А + Δ В + Δ Н = (+2) + (+11) + (+4) = +17

revealed a vector of positive direction.

Patient Yu was given recommendations on lifestyle modification - weight loss through aerobic physical activity (exercise in the gym daily for tolerance, but not less than 60 minutes), caloric intake (~ 1200 kcal / s with restriction of easily digestible carbohydrates). Prescribed drug therapy - overcoming and eliminating insulin resistance (metformin 1700 mg / day), antihypertensive therapy (enalapril maleate 2.5 mg / s) with dose adjustment according to blood pressure, hypolipidemic therapy (rosuvastatin 20 mg / day), with dose adjustment according to indicators of the lipid spectrum.

Six months later, against the background of the recommendations being followed and the decrease in body weight, positive trends were noted in laboratory parameters (Table 11), blood pressure 130/75 mm. rt. Art. According to instrumental methods (ECG, ECHO-CS, ophthalmoscopy), laboratory markers of renal function (GFR - 89 ml / min / 1.73 m ² , daily albumin loss - 0.4 mg / 24 hours, albumin-creatinine ratio <3 mg / mmol), no signs of vascular lesions were found.

The calculation of the risk of developing angiopathies was performed:

Δ A = (A ₁ - A ₁ *) + (A ₂ - A ₂ *) = (+1 point) + (+1 point) = +2 points

Δ B = (B ₁ - B ₁ *) + (B ₂ - B ₂ *) + (B ₃ - B ₃ *) + (B ₄ - B ₄ *) + (B ₅ - B ₅ *) + (B ₆ - V ₆ *) + (V ₇ - V ₇ *) + (V ₈ - V ₈ *) + (V ₉ - V ₉ *) + (V ₁₀ - V ₁₀ *) + (V ₁₁ - V ₁₁ * ) + (B ₁₂ - B ₁₂ *) + (B ₁₃ - B ₁₃ *) + (B ₁₄ - B ₁₄ *) = (+1 point) + (+1 point) + (+1 point) + (+1 point) + (+1 point) + (+1 point) + (0 point) + (+1 point) + (+1 point) + (+1 point) + (+1 point) + (+1 point) + (0 points) + (0 points) = +11 points

Δ H = (H ₁ - H ₁ *) + (H ₂ - H ₂ *) + (H ₃ - H ₃ *) + (H ₄ - H ₄ *) + (H ₅ - H ₅ *) + (H ₆ - H ₆ *) + (H ₇ - H ₇ *) + (H ₈ - H ₈ *) + (H ₉ - H ₉ *) = (0 points) + (0 points) + (0 points) + ( 0 points) + (0 points) + (+1 point) + (0 points) + (0 points) + (+1 point) = +4 points.

Estimated Risk of Vascular Lesions at 6 Months

Δ A + Δ B + Δ H = (+2) + (+11) + (+2) = +15

revealed a positive vector, with a tendency towards a decrease in the risk of developing vascular lesions in comparison with the baseline.

A year later, the patient took measures to change her lifestyle - she worked out in the gym, changed her dietary structure, as a result, a decrease in body mass index, waist circumference, blood pressure within the target values was noted, no deviations were found in biochemical and hemostasiological indicators (Table 12 ). According instrumental techniques (ECG, ECHO-CC ophthalmoscopy), laboratory markers of renal function (glomerular filtration rate - 82 mL / min / 1.73 m ^2, the daily loss of albumin - 0.12 mg / 24 hours, albumin-creatinine ratio <3.4 mg / mmol), no signs of vascular lesions were found.

The calculation of the risk of developing angiopathies was performed:

Δ A = (A ₁ - A ₁ *) + (A ₂ - A ₂ *) = (0 points) + (0 points) = 0 points

Δ B = (B ₁ - B ₁ *) + (B ₂ - B ₂ *) + (B ₃ - B ₃ *) + (B ₄ - B ₄ *) + (B ₅ - B ₅ *) + (B ₆ - V ₆ *) + (V ₇ - V ₇ *) + (V ₈ - V ₈ *) + (V ₉ - V ₉ *) + (V ₁₀ - V ₁₀ *) + (V ₁₁ - V ₁₁ * ) + (B ₁₂ - B ₁₂ *) + (B ₁₃ - B ₁₃ *) + (B ₁₄ - B ₁₄ *) = (0 points) + (0 points) + (0 points) + (0 points) + ( 0 points) + (0 points) + (0 points) + (0 points) + (0 points) + (0 points) + (0 points) + (0 points points) + (0 points) + (0 points) = 0 points

Δ H = (H ₁ - H ₁ *) + (H ₂ - H ₂ *) + (H ₃ - H ₃ *) + (H ₄ - H ₄ *) + (H ₅ - H ₅ *) + (H ₆ - H ₆ *) + (H ₇ - H ₇ *) + (H ₈ - H ₈ *) + (H ₉ - H ₉ *) = (0 points) + (0 points) + (0 points) + ( 0 points) + (0 points) + (0 points) + (0 points) + (0 points) + (0 points) = 0 points.

Estimated risk of vascular lesions after one year:

Δ A + Δ B + Δ H = (0) + (0) + (0) = 0 points.

Four years later, the body mass index, waist circumference, blood pressure, biochemical and hemostasiological parameters correspond to prognostically safe values (Table 13).

According to instrumental methods (ECG, ECHO-CS, ophthalmoscopy), laboratory markers of renal functions (GFR - 92 ml / min / 1.73 m ² , daily albumin loss - 0.2 mg / 24 hours, albumin-creatinine ratio <3 mg / mmol), no signs of vascular lesions were found.

The calculation of the risk of developing angiopathies was performed:

Δ A = (A ₁ - A ₁ *) + (A ₂ - A ₂ *) = (0 points) + (0 points) = 0 points

Δ B = (B ₁ - B ₁ *) + (B ₂ - B ₂ *) + (B ₃ - B ₃ *) + (B ₄ - B ₄ *) + (B ₅ - B ₅ *) + (B ₆ - V ₆ *) + (V ₇ - V ₇ *) + (V ₈ - V ₈ *) + (V ₉ - V ₉ *) + (V ₁₀ - V ₁₀ *) + (V ₁₁ - V ₁₁ * ) + (B ₁₂ - B ₁₂ *) + (B ₁₃ - B ₁₃ *) + (B ₁₄ - B ₁₄ *) = (0 points) + (0 points) + (0 points) + (0 points) + ( 0 points) + (0 points) + (0 points) + (0 points) + (0 points) + (0 points) + (0 points) + (0 points points) + (0 points) + (0 points) = 0 points

Δ H = (H ₁ - H ₁ *) + (H ₂ - H ₂ *) + (H ₃ - H ₃ *) + (H ₄ - H ₄ *) + (H ₅ - H ₅ *) + (H ₆ - H ₆ *) + (H ₇ - H ₇ *) + (H ₈ - H ₈ *) + (H ₉ - H ₉ *) = (0 points) + (0 points) + (0 points) + ( 0 points) + (0 points) + (0 points) + (0 points) + (0 points) + (0 points) = 0 points.

Estimated risk of vascular lesions after four years:

Δ A + Δ B + Δ H = (0) + (0) + (0) = 0 points.

Thus, the implementation by the patient Yu of the recommendations on changing her lifestyle with the achievement of prognostically safe anthropometric, biochemical, hemostasiological values helped to minimize the risk of developing vascular lesions and did not lead to the formation of angiopathies over a four-year follow-up period.

LITERATURE

1. International Diabetes Foundation (IDF). The IDF consensus worldwide definition of metabolic syndrome. Accessed 2017.http: //www.diabetesatlas.org/

2. Brownlee, M. The pathobiology of diabetic complications // Diabetes. - 2005. - V. 54. - P. 1615-1625.

3. Peters-Harmel, E. Diabetes mellitus: diagnosis and treatment / E. Peters-Harmel, R. Mathur. Per. from English. - M .: Practice, 2008 .-- 496 p.

4. Beckham, J.H. Diabetes and atherosclerosis: epidemiology, pathophysiology and management / J.H. Beckham, M.H. Creager, P. Libby [et al.] // JAMA. - 2002. - V. 287. - P. 2570-2581.

5. Juutilainen, A. Type 2 diabetes as a coronary heart disease equivalent. An 18-year prospective population-based study in Finnish subjects / A. Juutilainen [et al.] // Diabetes Care. - 2005. - V. 28. - P. 2901-2907.

6. Graham I. et al. European Atherosclerosis Society (EAS). European guidelines on cardiovascular disease prevention in clinical practice: full text. Fourth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice / I. Graham et al. // Eur. J. Cardiovasc. Prev. Rehabil. - 2007. - Vol. 14 Suppl 2. - S1-113.

7. Algorithms for specialized care for patients with diabetes mellitus / Ed. I.I. Dedova, M.V. Shestakova, A. Yu. Mayorov. - 9th edition. - M .: UP PRINT, 2019 - P. 79.

8. Conroy R.M. et al. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project / R.M. Conroy et al. // Eur. Heart J. - 2003. Vol. 24, N11. - P. 987-1003.

9. National recommendations "Cardiovascular prevention 2017" - Moscow, 2017 - 289 p.

10. Titz N. Clinical guidelines for laboratory tests. UNIMED-press Russia. - 2003 .-- 960 s.

Claims (1)

A method for predicting the risk of developing vascular lesions in the early stages of carbohydrate metabolism disorders, including taking venous blood, determining the level of cholesterol, characterized in that, in addition, the complex determines the deviation of anthropometric parameters (A), including body mass index (BMI), kg / m ² , (A ₁ ); waist circumference, cm, (A ₂ ), take into account prognostically safe values A ₁ * <25 kg / m ² and A ₂ * <80 cm in women, <94 cm in men, respectively, biochemical parameters (B) - fasting plasma glucose, mmol / l, (B ₁ ); glycated hemoglobin (HbA1c),%, (В ₂ ); insulin resistance index (HOMA-IR), units, (B ₃ ); total cholesterol (TC), mmol / l, (B ₄ ); low density lipoprotein cholesterol (LDL-C), mmol / l, (B ₅ ); triglycerides (TG), mmol / l, (B ₆ ); high density lipoprotein cholesterol (HDL-C), mmol / l, (B ₇ ); low-density lipoprotein cholesterol (cholesterol-non-HDL), mmol / l, (B ₈ ); alpha ₂ -globulins, g / l, (B ₉ ); beta ₁ -globulins, g / l, (B ₁₀ ); C-reactive protein (CRP), mg / L, (B ₁₁ ), uric acid, μmol / L, (B ₁₂ ); creatinine (B ₁₃ ), μmol / L, alanine amino transferase (ALT), μkat / L, (B ₁₄ ), aspartate aminotransferase (ACT), μkat / L, (B ₁₅ ), take into account prognostically safe values - B ₁ * <6 , 1 mmol / L, B ₂ * <6.0 mmol / L, B ₃ * <2.5, B ₄ * <4.5 mmol / L, B ₅ * <2.5 mmol / L, B ₆ * <1.7 mmol / L, B ₇ *> 1.0 mmol / L in men,> 1.3 mmol / L in women, B ₈ * <3.4 mmol / L, B ₉ * <9.0 g / l, V ₁₀ * <10.6 g / l, V ₁₁ * <5 mg / l, V ₁₂ * <339 μmol / l, V ₁₃ * <40 μkat / l, B _14, * <40 μkat / l , hemostasis - mean platelet volume, fl (H ₁ ), intensity of ADP- and collagen-induced platelet aggregation,%, (H ₂ and H ₃ ), AhTT, c (H ₄ ), fibrinogen, g / L, (H ₅ ), activity of factor VII,%, (H ₆ ), antithrombin III,%, (H ₇ ), plasminogen%, (H ₈ ), endothelin, pmol / l, (H ₉ ), take into account prognostically safe values - H ₁ * <10 fl, H ₂ * <64%, H ₃ * <60%, H ₄ *> 23 s, H ₅ * <4 g / l, H ₆ * <110%, H ₇ *> 70%, H ₈ *> 80%, H ₉ * <0.16 pmol / l, respectively, then the difference between the patient's parameters and the prognostic and safe values (A ₁ -A ₁ *), (A ₂ -A ₂ *); (B ₁ -B ₁ *), (B ₂ -B ₂ *), (B ₃ -B ₃ *), (B ₄ -B ₄ *), (B ₅ -B ₅ *), (B ₆ -B ₆ *), (V ₇ -V ₇ *), (V ₈ -V ₈ *), (V ₉ -V ₉ *), (V ₁₀ -V ₁₀ *), (V ₁₁ -V ₁₁ *), ( B ₁₂ -B ₁₂ *), (B ₁₃ -B ₁₃ *), (B ₁₄ -B ₁₄ *); (H ₁ -H ₁ *), (H ₂ -H ₂ *), (H ₃ -H ₃ *), (H ₄ -H ₄ *), (H ₅ -H ₅ *), (H ₆ -H ₆ *), (H ₇ -H ₇ *), (H ₈ -H ₈ *), (H ₉ -H ₉ *), respectively, and with a positive value of each of An-An *, Bn-Bn *, Hn- Hn * is given 1 point, if they are zero or negative, they are given 0 points, the total number of points (K) is determined as the sum of all points, and if the sum is positive, the risk of developing vascular lesions is determined, and if it is zero, it is absent.