The method of choice drugs in the treatment of hypertension in patients with obesity

 

(57) Abstract:

The invention relates to medicine. The method of choice drugs in the treatment of hypertension in patients with obesity, including glucose tolerance test and depending on the results of the test - the purpose of the biguanides, or agonists 1-imidazoline receptors. The method allows for the treatment to take into account the sensitivity of tissues to insulin. table 1.

The invention relates to medicine, namely to therapy, and can be used in the treatment of hypertensive disease (HD) in patients with obesity.

There is a method of drug selection for the treatment of hypertension, according to which it is recommended to start therapy with a destination of beta-blockers or saluretics, and when their inefficiency move to combination therapy (World Health organization - International Society of hypertension. // J. Hypertens 1999. 17: 151-185.) This method is adopted for the prototype.

However, the known method of choice drugs in the treatment of GB does not take into account the role of insulin resistance and hyperinsulinemia, which are some of the key causes of hypertension in patients with obesity. The purpose of beta biomaterial the impact of these drugs on carbohydrate and lipid metabolism, even with relatively short-term treatment (3-6 months).

The basis of the invention is to create a method of choice drugs in the treatment of GB patients who are obese, take into account such an important link in the pathogenesis of hypertension, as the sensitivity of tissues to insulin.

The problem is solved in that in the method of selection of drugs for the treatment of hypertension in patients with obesity, according to the invention, carried out a standard glucose tolerance test (SGT) determine glucose tolerance and insulin levels in fasting blood via regular intervals, calculate the indicator "area under the curve of insulin (PKI), and with the increased rate of PCI and normal glucose tolerance prescribed agonists 1-imidazoline receptor, and with the increased rate of PCI and disturbed glucose tolerance or diabetes mellitus (DM) Type II prescribed drugs from the group of biguanides.

Conducting the standard glucose tolerance test, determination of glucose tolerance and insulin levels in fasting blood via regular intervals, the calculation of PKI allows you to select bolney or progression of insulin resistance. Index of PCI on the background SGT has high information content and reproducibility and at the same time allows you to get information that is comparable to the results applicationscope hyperinsulinemia clamp.

Were studied 133 patients with GB combined with obesity. In all the examined patients past history, there were no instructions on carbohydrate metabolism. When conducting a standard glucose tolerance test revealed that 68% of patients with obesity occurred in varying degrees, expressed disorders of carbohydrate metabolism (table).

Insulin resistance, according to the results of the calculation of PCI, was detected in 78% of the surveyed patients.

The method is as follows.

Determine the level of glucose in the serum capillary fasting blood after a 16-hour fast and through the standard time intervals of 30, 60, 90, 120 min after ingestion of 75 g of dry glucose dissolved in 200 ml of water. In parallel, determine the level of immunoreactive insulin in venous blood using sets RIO-Ann-PG-125J (State enterprise "Self-supporting pilot production of the Institute of Bioorganic chemistry, Academy of Sciences of the Republic of Belarus", the ode to the sum of the trapezoids on the background of standard glucose tolerance test (GTT) with a parallel study of the level of insulin in the blood serum (described in detail in the work Seltzer N., Aller W., Herron , A., Brennan, M. "Insulin secretion in response to glucemic stimulus" // J. Clin Invest.- 1967. - V 46. - p. 323-330).

PCI = 1/2 x (I - IO) x 30 + IO x 30 + 1/2 x (I - I) x 30 + Y x 30 + 1/2 x (I - I) x 60 + I x 60 where:

IO - the level of insulin on an empty stomach,

I, I, I - insulin levels in the blood after 30, 60, 120 min after glucose load, respectively.

With the increased rate of PKI (the normal rate of PKI according to the literature data is 3857,28 494,76 mkme/min/ml) and normal glucose tolerance prescribed agonists 1-imidazoline receptor, and with the increased rate of PCI and disturbed glucose tolerance or diabetes mellitus type II prescribed drugs from the group of biguanides.

The method is illustrated by the following examples.

Example 1. Patient Z. 44 years, were examined in the clinic of internal medicine in January 1998 From the anamnesis it is known that obese 30 years; with 39 notes increased numbers of blood pressure (BP), presence of diabetes prior to admission to the clinic did not know. The burdened heredity, the closest relatives of obese.

During examination: height 176 cm, weight 114 kg, body mass index (BMI) 36.7 kg/m2; the ratio of waist circumference and hip circumference (FROM/ON the left of 14400 mkme/min/ml, the indicator "area under the curve of glucose" (PCG) was 1560 mmol/l

Diagnosis: Body obesity II Art. Hypertension Art. II diabetes mellitus type II.

After the examination, the patient was assigned to a diet of 1000 kcal per day and the drug from the group of derivatives of biguanide - gliformin (Metformin) at a daily dose of 1.5 Gy. (500 mg three times a day) for 3 months.

With the re-examination after three months the patient body weight decreased by 10 kg and was 104 kg; BMI of 33.5 kg/m2; ratio of FROM ABOUT decreased and amounted to 0.94; decreased the blood pressure to 140/90 mm RT.article When re-GTT indicators of carbohydrate metabolism fully normalized: significantly decreased the integral indicator PKG -1197 mmol/l, and more than a third of the decreased rate of PCI and was 9128,4 mkme/min/ml

Example 2. Patient K., 51. The patient was examined in the clinic of internal medicine in November 1997 From the anamnesis it is known that excessive weight to 40 years. About 10 years (41 years) knows about raising HELL, regular treatment is not received. The burdened heredity: the mother suffered from obesity and arterial hypertension.

During examination: height 164 cm, weight 88 to Italy SGT - within limits, the rate of PCI was 5640 mkme/min/ml, the integral indicator PKG - 1031 mmol/l

Diagnosis: Chudovishnoe obesity I Art. Hypertension II Art.

After the examination, the patient was assigned to a diet of 1000 kcal per day and treatment with moxonidine (CENT) (Eli Lilly, registration number 006359/07.08.95; 009749/30.09.97) - agonist 1-imidazoline receptors in a daily dose of 0.6 mg

A repeat survey was conducted 6 months after the appointment Zinta. The weight of the patient has not changed and amounted to 86 kg, BMI 32 kg/m2. The ratio of FROM ABOUT remained the same; HELL decreased to 140/80 mm RT.article; figure PKG did not change significantly, while the rate of PCI decreased significantly and amounted 4960 MK IU/min/ml

According to the proposed method has been selected group of patients (30 men) who had treatment with moxonidine in individually podobrannoj dose (0.2 to 0.6 g per day) for 6 months. In patients with GB was observed not only distinct hypotensive effect (systolic blood pressure decreased from 152,83,9 to 1423,6; diastolic blood pressure with 93,62,4 to 85,01,9 mm RT.art., p < 0.005 percent), but significantly improved insulin sensitivity (28 out of 30, i.e. 93% of patients). So, during SGT on the 9,016,5 MK U/ml, respectively, p > 0.05) and a significant decrease in the level of insulin at 120 min of the test (with 57,710,3 to 38,96,8 MK U/ml, p < 0,05). Index of PCI before treatment was 5865,27324,52 mkme/min/ml, and after 6 months of continuous Cinta - 4965,84286,41 mkme/min/ml With significant changes in the blood glucose level is not observed. The reduction of insulin levels in the blood correlated with improvement in hemodynamics (marked decrease in total peripheral vascular resistance with 2312,6119,0 Dyne/s/cm to 1864,5109,2 Dyne/s/cm, p < 0,001 without changing the minute volume of blood), as well as the reduction in the degree of left ventricular hypertrophy. Since the index of mass of the left ventricle decreased from 131,27,3 g/m to 124,25,4 g/m (p > 0.05), and the thickness of the posterior wall of the left ventricle decreased from 1,590,03 cm to 1,470,03 cm (p < 0,05). Under the influence of treatment Cincom according to occlusive plethysmography combined with the volumetric rate of flow increased with 2,840,7 to 3,750,75 ml/min/cm (p < 0,05), indicating that the decrease of vascular tone.

The other group (18 patients) in accordance with the proposed method was prescribed medication from the group of biguanides - gliformin (Akrikhin, Russia, registration number R.1019.9 from 30.06.85) in a daily dose of 1.5 Gy. Derivatives of biguanides was administered based on protivopokazan the x biguanides, apart from reducing body weight showed a significant decrease of systolic blood pressure (174,59,8 to 142,64,3 mm RT.cent.). On the background of treatment with biguanides happened normalization of parameters of glycemic profile - estimated value PKG decreased from 1546,94107,59 mmol/l to 935,67182,36 mmol/l (p < 0.05), and decrease and normalization of insulin levels in the blood, improved lipid profile and decreased insulin resistance is an indicator of PCI decreased from 10669,451128,37 mkme/min/ml to 6663,031515,14 mkme/min/ml in all patients (100%). Correlation analysis showed that the relationship dynamics of systolic blood pressure and insulin sensitivity in patients treated with gliformin.

Using the proposed method allows you to make a choice drugs in the treatment of GB in patients with obesity, taking into account such an important part of the pathogenesis of arterial hypertension, as the sensitivity of tissues to insulin.

The method of choice drugs in the treatment of hypertension in patients with obesity, characterized in that conduct standard glucose tolerance test, determine glucose tolerance and insulin levels in fasting blood via regular intervals, calculate the indicator "n the STI to glucose appoint agonists I-imidazoline receptors, and with the increased rate of "area under the curve of insulin and disturbed glucose tolerance or diabetes mellitus type II prescribed drugs from the group of biguanides.

 

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