RU2533836C1 - Method for monitoring individuals with risk of early atherosclerosis and suffering from type 2 diabetes mellitus - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: clinical medical history data are determined as follows: body weight index (BWI), kg/m²; waist circumference (WC), hip circumference (HC), waist-to-hip ratio, type 2 diabetes mellitus diagnosed in close relatives, arterial hypertension (AH) diagnosed. The laboratory data are measured as follows: plasminogen activator inhibitor-1 (PGAI-1), nmole/l; nitrogen oxide (NO) metabolites, %; resistin, ng/ml; insulin resistance (IR), mIU/ml; triglycerides (TG), mmole/l; high density lipoprotein cholesterol (HDLPC), mmole/l; fibrinogen, mg/dl; impaired fasting glucose (IFG), mmole/l; glycosylated haemoglobin (HbAlc), %; impaired glucose tolerance (IGT), mmole/l; homocystein (HC), mcmole/l; TNF-α, pg/ml; C-reactive protein, mg/l; endothelin and fibrinogen. The derived values are scored. The total score is used to determine a risk of atherosclerosis in the patients suffering from type 2 diabetes mellitus: extremely high, high, moderate and low. Taking into account the detected degree of risk, a dosage of aspirin and statins are determined, as well as a monitored mode of blood lipids, urinary albumin and blood creatinine is specified.

EFFECT: method enables determining a degree of risk of the atherosclerosis progression as shown by the clinical medical history and laboratory data, as well as specifying individual pathogenetic therapy for the patient that leads to reducing developing cardiovascular complications.

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Description

The invention relates to medicine, namely to internal medicine.

Type 2 diabetes mellitus (DM) is one of the main independent risk factors for atherosclerosis. Moreover, according to the European recommendations for the treatment of dyslipidemia, cardiovascular risk is understood as the probability of a patient having cardiovascular disease (CVD) due to the development of atherosclerosis over a certain period. There are a number of CVD risk assessment systems, of which the most famous are the Framingham Risk Assessment Scale, SCORE (Systemic Coronary Risk Assessment), ASSIGN (Scottish Risk Assessment Model), PROCAM (Prospective Munster Cardiovascular Research) and WHO (World Health Organization) . At the same time, patients suffering from type 2 diabetes mellitus or type 1 diabetes mellitus with microalbuminuria automatically belong to the group of VERY HIGH or HIGH risk.

However, due to the latent onset of type 2 diabetes, the erasure of the clinical picture, in half of patients the disease is detected after 7-12 years from its onset. In addition to hyperglycemia, which is considered as the main risk factor for complications of diabetes mellitus, there are other factors whose presence can accelerate the development and progression of angiopathies in patients with diabetes mellitus. A number of studies, including the MONICA study, have shown that classical risk factors for the development of atherosclerosis cannot fully explain the development of cardiovascular complications, as their prevalence is about 15% in women and 40% in men. As a result of this, the search for other causes of atherothrombosis continues intensively (Ametov A.S., 2005; Chazov E.I., 2007).

Today, there is no doubt that the important role in the pathogenesis of vascular damage and atherosclerosis is played by homocysteine, C-reactive protein (CRP) and fibrinogen circulating in the blood (Shevchenko O.P., 2004; Bondar I.A., 2007; Lyusov V .A., 2007; Zvereva I.V., 2009; Gireyev E.Yu., 2010; Dreval A.V., 2010; Morkovskikh N.V., 2010; Bataille R., 1992; Gook D., 2000; Bhatt DL 2008). However, despite the unconditional effect of many biochemical parameters on the pathogenesis of atherosclerosis in diabetes mellitus, many clinical studies note the absence of a correlation of obvious clinical manifestations with the level of specific markers of the development of atherosclerosis. For example, in a study by S.A. Burov et al. There was no relationship between obesity and resistin levels and tumor necrosis factor α (TNF α).

Achievable technical result is the provision of individual monitoring of individuals at risk of early development of atherosclerosis in patients with type 2 diabetes.

Based on the foregoing, we developed a method for assessing the degree of risk of developing atherosclerosis, taking into account the following indicators: plasminogen activator inhibitor-1 (IAPH-1), NO - nitric oxide metabolites, resistin, insulin resistance (IR), TG - triglycerides, HDL cholesterol, fibrinogen, BMI - body mass index, NGN - impaired fasting glucose HbAlc, NTG - impaired glucose tolerance, HC - homocysteine, TNF-α, C-RB.

To develop a new method for assessing the risk of developing atherosclerosis in patients with type 2 diabetes, we examined patients with type 2 diabetes mellitus of moderate and severe severity. The diagnosis of diabetes mellitus (DM) was made according to the International Classification of Diseases X-Revision (ICD-10), prepared by the World Health Organization (WHO, Geneva, 1992).

All patients (table 1) were evaluated anthropometric data, which included measuring height, determining body weight, waist circumference and hips to determine body mass index (BMI) and the ratio of the waist circumference to the circumference of the hips (OT / V). Carbohydrate metabolism was evaluated by fasting glucose, glycated hemoglobin (HbAlc), insulin resistance, impaired glucose tolerance.

To calculate insulin resistance (IR), we used a small model of homeostasis with the determination of the HOMA-IR index (D. Metthews et al., 1985), as well as impaired glucose tolerance (NTG). Assessment of the blood lipid spectrum included determination of total cholesterol (OXC), high density lipoprotein cholesterol (HDL cholesterol), triglycerides (TG). In addition, the level of fibrinogen, an inhibitor of plasminogen-1 activator (IAPH-1), NO - metabolites of nitric oxide, resistin, HC - homocysteine, TNF-α, and CRP were determined in all patients.

Table 1 The main clinical and laboratory parameters in patients with type 2 diabetes. Indicator Units Value Body Mass Index (BMI) kg / m ² 32,4 The ratio of the waist circumference to the circumference of the hips (OT / O) cm 1.05 Fasting glucose (IAT) mmol / l 9.61 Insulin Resistance (IR) mIU / ml 16.14 Impaired glucose tolerance (NTG) mmol / l 6.16 Glycated Hemoglobin (HbAlc) % 9.26 HDL cholesterol mmol / l 0.84 Triglycerides (TG) mmol / l 2.18 Tissue plasminogen activator-1 inhibitor (IAP-1) nmol / l 1.31 Fibrinogen mg / dl 397.6 Endothelin fmol / ml 0.37 Resistin ng / ml 19.85 Nitric Oxide Metabolites (NO) % 38.66 Homocysteine μmol / l 32.13 Tumor Necrosis Factor (TNF-α) pg / ml 8.7 C-reactive protein (CRP) mg / l 5.36

To assess the complex effect of various clinical and biochemical parameters on the development of atherosclerosis in patients with type 2 diabetes, as well as to establish the most important predictors that affect the development of atherogenic vascular lesions, a multiple regression analysis was performed. For this, a matrix of the dependence of the main parameters of atherosclerosis (triglycerides and HDL) in patients with type 2 diabetes and clinical and biochemical parameters was compiled, which were divided into 4 groups:

1. Clinical and anamnestic indicators: body mass index, heredity, the ratio of the waist circumference to the circumference of the hips and the presence of arterial hypertension.

Biochemical parameters

2. Carbohydrate metabolism: insulin resistance, impaired fasting glucose, impaired glucose tolerance, glycated hemoglobin.

3. Hormonal and metabolic parameters: fibrinogen, tissue plasminogen activator-1 inhibitor (IAP-1), resistin and homocysteine.

4. Pro-inflammatory: metabolites of nitric oxide (NO), CRP, TNF, endothelin.

According to the regression analysis, it was found that the level of triglycerides, which determines the risk of developing atherosclerosis in patients with type 2 diabetes, depended on the level of all the indicators presented, with greater severity from endothelin, impaired fasting glucose, plasminogen, resistin and the ratio of the waist circumference to the hip circumference, and HDL cholesterol was inversely related to all indicators, with greater severity from endothelin, impaired fasting glucose, plasminogen, and the ratio of the waist circumference to the hip circumference.

According to cluster analysis, clusters were formed by the degree of proximity of the selected criteria. Based on this, a risk assessment scale is proposed. The most significant criteria received 4 points, less significant 1, 2, 3, respectively (table 2).

table 2 The risk assessment scale for the development of early atherosclerosis in patients with type 2 diabetes Estimated Parameter Points Clinical and anamnestic data one BMI 26.5 and more one 2 OT / V 0.66-0.67 2 0.97-1.05 3 1.15-1.21 four 3 Heredity (type 2 diabetes in close relatives) 2 four Arterial hypertension (AH) (140/90 mmHg or more) - presence one Carbohydrate metabolism 5 Insulin resistance less than 15.90 one 15.91-18.65 2 More than 18.66 3 6 Fasting glucose Less than 8.82 2 8.83-9.30 3 More than 10.74 four 7 Glycated hemoglobin Less than 9.49 one 9.50-11.62 2 More than 11.63 3 8 Impaired glucose tolerance Less than 6.20 one More than 6.21 2 9 Nitric oxide (NO) Less than 40.10 one More than 40.11 2 10 Tumor Necrosis Factor α Less than 8.37 one More than 8.38 2 eleven C-reactive protein More than 1.90 one 12 Endothelin less than 0.33 one More than 0.34 four 13 Resistin Less than 8.02 one 8.03-20.60 3 More than 20.61 four fourteen Fibrinogen More than 287.84 one fifteen Homocysteine Over 21,40 one

According to the obtained cluster analysis, we can calculate the risk of developing atherosclerosis in patients with type 2 diabetes, taking into account specific indicators: plasminogen activator-1 inhibitor (IAPH-1), NO - nitric oxide metabolites, resistin, insulin resistance (IR), TG - triglycerides, HDL cholesterol, fibrinogen, BMI - body mass index, NGN - impaired fasting glucose, HbAlc, NTG - impaired glucose tolerance, HC - homocysteine, TNF-α, C-RB.

The described model for practical use is presented in the form of a table, it is enough for the doctor to enter the values of the above indicators in this table to get a conclusion about the degree of risk of developing atherosclerosis.

The method is as follows.

Clinical history data are determined: body mass index (BMI), kg / m ² ; waist circumference (OT), hip circumference (OB), OT / OB ratio, the presence of type 2 diabetes in close relatives, the presence of arterial hypertension (AH). Laboratory data are determined: the level of plasminogen activator-1 inhibitor (IAPH-1), nmol / l; metabolites of nitric oxide (NO),%; resistin, ng / ml; insulin resistance (IR), mIU / ml; triglycerides (TG), mmol / l; high density lipoprotein cholesterol (HDL cholesterol), mmol / l; fibrinogen, mg / dl; impaired fasting glucose (NGN), mmol / l; glycated hemoglobin (HbAlc),%; impaired glucose tolerance (NTG), mmol / l; homocysteine (HC), mcmol / l; TNF-α, pg / ml; C-reactive protein, mg / l; endothelin and fibrinogen.

The obtained values are assigned scores according to table 2. The identified scores are summarized and concluded on the degree of risk of developing atherosclerosis in patients with type 2 diabetes:

26 points or more - an extremely high risk;

20-25 points - high risk,

from 14 to 19 points - medium risk,

below 14 points - low risk.

According to the obtained scale for assessing the risk of early development of atherosclerosis, we have developed recommendations for monitoring patients with type 2 diabetes.

1. All patients, along with the treatment of the underlying disease (type 2 diabetes), lifestyle changes and the nature of nutrition, the following is recommended.

To reduce the frequency of micro- and macrovascular complications associated with atherosclerosis, correction of lipid metabolism disorders is necessary. Therefore, according to the recommendations of the International Federation of Diabetologists and the European Bureau of the World Health Organization, it is advisable to conduct a lipid metabolism study every six months, but at least once a year. When treating with statins in high doses, the frequency of lipid metabolism studies increases to 1 time in 2-3 months to control the effectiveness of the drugs taken. In addition, to prevent the development and rapid progression of diabetic kidney damage, it is necessary to actively identify the early stages of diabetic nephropathy, since it is diabetic nephropathy that is currently the leading cause of high disability and mortality in patients with diabetes mellitus. The earliest criterion for the development of diabetic nephropathy (before the appearance of proteinuria) is microalbuminuria. Given the daily fluctuations in albumin excretion, to confirm true microalbuminuria, it is necessary to have at least two positive results for 4-6 months. At the same time, an annual screening for diabetic nephropathy is necessary for patients with type 2 diabetes mellitus from the time of diagnosis of diabetes mellitus.

2. According to the recommendations of the American Diabetes Association (ADA), the appointment of acetylsalicylic acid is indicated for all patients with type 2 diabetes for the secondary prevention of coronary heart disease. Aspirin should be prescribed in a daily dose of up to 76-162 mg.

According to the EASD / European Society of Cardiologists Guidelines for Diabetes / Cardiovascular diseases, continuous treatment with statins should be prescribed for most patients with type 2 diabetes (Shestakova M.V. Endocrinologist's comments on the Recommendations for diabetes mellitus, prediabetes and cardiovascular diseases ESC-EASD 2007 / “Diabetes mellitus” 2008, No. 1, pp. 97-99). In this case, the most appropriate is the individual selection of a dose of statins, based on the degree of risk of developing atherosclerosis. High doses are suggested to be left only to people at a very high risk for faster achievement of target cholesterol levels (MN Davidson, J.G. Robinson. Safety of Aggressive Lipid Management. J Am Coil Cardiol 2007; 49: 1753-62).

Table 3 A differentiated approach to the diagnosis and treatment of the development of early atherosclerosis in patients with type 2 diabetes The degree of risk of developing early atherosclerosis Screening Treatment 1) determination of the lipid spectrum of the blood 1 time in 3 months extremely high risk of developing atherosclerosis 2) determination of urinary albumin excretion and blood creatinine index at least 1 time in 6 months 1) aspirin (75-162 mg / day) 2) statins (in high doses - up to 80 mg / day) 1) determination of the lipid spectrum of the blood 1 time in 6 months high risk of developing atherosclerosis 2) determination of urinary albumin excretion and blood creatinine index at least 1 time in 6 months 1) aspirin (75-162 mg / day) 2) statins (in average doses - 20-40 mg / day) 1) determination of the lipid spectrum of blood at least 1 time in 6 months medium risk of developing atherosclerosis 2) determination of urinary albumin excretion and blood creatinine index 1 time in 12 months 1) aspirin (75-162 mg / day) 2) statins (in the minimum dose - no more than 10 mg / day) 1) determination of the lipid spectrum of the blood 1 time in 12 months low risk of developing atherosclerosis 2) determination of urinary albumin excretion and blood creatinine index at least 1 time in 12 months 1) aspirin (75-162 mg / day)

2. As a treatment for hypertension, preference should be given to drugs from the groups:

A) Angiotensin-converting enzyme inhibitors (ACE inhibitors) or

B) Angiotensin II receptor antagonists.

Clinical example

Example. B-naya N., 43 years old. Diagnosis: Type 2 diabetes mellitus, moderate course, exacerbation.

Deterioration of health over the past 1.5 months. Complaints of weakness, dizziness, irritability. The diagnosis of diabetes was made a year ago. Notes the presence of type 2 diabetes in mom.

Objectively: height 162 cm, weight - 63 kg. BMI is 24, the ratio of waist to hip circumference is 0.97. The right physique. The skin and visible mucous membranes are clean. The tongue is wet, clean. Lungs - vesicular breathing. Heart - clean, rhythmic tones. Pulse - 70 / min, AD-120/80. The abdomen is soft, painless, the liver and spleen are not palpable. From the anamnesis it is known that the patient’s mother died of myocardial infarction.

Biochemical research

The level of triglycerides is 1.78, HDL cholesterol is 1.21; impaired fasting glucose - 8.4, impaired glucose tolerance - 5.8, insulin resistance - 13.8, glycated hemoglobin - 6.5; resistin - 27.5, fibrinogen - 426.87, homocysteine - 32.4, NO - 45.6, TNF - 8.2, CRP - 7.5, endothelin - 0.33, plasminogen - 0.5.

The obtained values are substituted in table 2 and calculate the indicator that determines the degree of risk of developing atherosclerosis.

Table 4 The scale for assessing the risk of early development of atherosclerosis in patient N. Clinical and anamnestic data BMI Less than 26.5 (24) 0 OT / V 0.97-1.05 (0.97) 3 Heredity 2 Arterial hypertension 0 Carbohydrate metabolism Insulin resistance over 13.71 (13.8) 2 Fasting glucose 8.83-9.30 (8.4) 3 Glycated hemoglobin Less than 6.50 (6.5) one Impaired glucose tolerance Less than 6.20 (5.8) one Nitric oxide (NO) 2 More than 40.11 Tumor Necrosis Factor α Less than 8.37 (8.2) one C-reactive protein one Over 1.9 (7.5) Endothelin one Less than (0.33) Resistin Over 20.61 (27.5) four Fibrinogen More than 287.84 (426.85) one Homocysteine Over 21.40 (32.4) one

Based on the use of the table developed by us, we calculate the degree of risk of developing atherosclerosis: 1 × 6 + 2 × 3 + 3 × 2 + 4 = 22.

Thus, the risk of developing atherosclerosis in this patient is assessed as high, and despite the fact that the patient has a normal blood lipid profile, according to the recommendations, the patient was additionally given nutrition recommendations, a follow-up plan was made, aspirin and statins were prescribed in the appropriate doses. After 6 months of observation, the lipid level of triglycerides was 1.68 mmol / L, which corresponds to the target level, initially it is necessary to reduce the concentration of triglycerides in the blood <150 mg / dl (1.7 mmol / L). The test for microalbumiuria is negative. It is recommended to continue the selected therapy and repeat the research results after 6 months.

Our proposed method allows us to determine the degree of risk of developing atherosclerosis, which is important in the clinical situation when the diagnosis is established based on the results of the lipid spectrum. In addition, the subsequent selection of treatment allows you to choose an individual pathogenetically substantiated therapy for the patient, which leads to a decrease in the development of cardiovascular complications.

Claims (1)

A method for monitoring individuals with a risk of early development of atherosclerosis and the presence of type 2 diabetes mellitus, including the determination of clinical and medical history data: body mass index (BMI), kg / m ² ; waist circumference (OT), hip circumference (OB), OT / OB ratio, the presence of type 2 diabetes mellitus in close relatives, the presence of arterial hypertension (AH), and laboratory data: level of plasminogen activator inhibitor-1 (IAPG-1), nmol / l; metabolites of nitric oxide (NO),%; resistin, ng / ml; insulin resistance (IR), mIU / ml; triglycerides (TG), mmol / l; high density lipoprotein cholesterol (HDL cholesterol), mmol / l; fibrinogen, mg / dl; impaired fasting glucose (NGN), mmol / l; glycated hemoglobin (HbAlc),%; impaired glucose tolerance (NTG), mmol / l; homocysteine (HC), mcmol / l; TNF-α, pg / ml; C-reactive protein, mg / l; endothelin and fibrinogen; the obtained values are assigned scores: BMI of 26.5 or more - 1 point; OT / AB: 0.66-0.67 - 2 points, 0.97-1.05 - 3 points, 1.15-1.21 - 4 points; the presence of type 2 diabetes in close relatives: 2 points; the presence of hypertension: 1 point; IR: less than 15.9 - 1 point, 15.91-18.65 - 2 points, more than 18.66 - 3 points; NGN: less than 8.82 - 2 points, 8.83-9.30 - 3 points, more than 10.74 - 4 points; HbAlc: less than 9.49 - 1 point, 9.50-11.62 - 2 points, more than 11.63 - 3 points; NTG: less than 6.20 - 1 point, more than 6.21 - 2 points; NO: less than 40.10 - 1 point, more than 40.11 - 2 points; TNF-α: less than 8.37 - 1 point, more than 8.38 - 2 points; C-reactive protein: more than 1.90 - 1 point; endothelin: less than 0.33 - 1 point, more than 0.34 - 4 points; resistin: less than 8.02 - 1 point, 8.03-20.60 - 3 points, more than 20.61 - 4 points; fibrinogen: more than 287.84 - 1 point; homocysteine: more than 21.40 - 1 point; the scores obtained are summarized and, with a total of 26 points or more, they determine the presence of an extremely high risk of developing atherosclerosis in patients with type 2 diabetes and, while receiving basic therapy, aspirin is additionally prescribed 75-162 mg / day and statins up to 80 mg / day, blood lipid spectrum monitoring 1 time in 6 months, and urinary albumin excretion and blood creatinine index - at least 1 time in 6 months; with a sum of 20-25 points, the presence of a high risk is determined and, against the background of basic therapy, aspirin 75-162 mg / day and statins 20-40 mg / day are additionally prescribed, the blood lipid spectrum is monitored once every 3 months, and albumin excretion in urine and blood creatinine - at least 1 time in 6 months; with a sum of 14 to 19 points, the presence of an average risk is determined and, against the background of basic therapy, aspirin is additionally prescribed 75-162 mg / day and statins - not more than 10 mg / day, blood lipid spectrum monitoring is carried out at least 1 time in 6 months, and urinary albumin excretion and blood creatinine - 1 time in 12 months; if the sum is below 14 points, the presence of low risk is determined and, against the background of basic therapy, aspirin is additionally prescribed 75-162 mg / day, the blood lipid spectrum is monitored once every 12 months, and urinary albumin and urine creatinine excretion are monitored at least 1 time at 12 months.