RU2054936C1 - Membrane-stabilizing agent for treatment of patient with insulin-dependent and insulin-independent diabetes mellitus - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: method involves the use of taurine as membrane-stabilizing agent both at insulin-dependent and insulin-independent diabetes mellitus that provides the significant improvement of patient state and stabilization of process course. EFFECT: enhanced effectiveness of treatment. 3 tbl

Description

 The invention relates to medicine, in particular to endocrinology, and can be used in clinical conditions for the treatment of patients with insulin-dependent and non-insulin-dependent diabetes mellitus.

 The literature contains data on the sugar-lowering effect of taurine in an experiment on a model of diabetes mellitus. This effect was found in an alloxan diabetes model in an acute experiment with a taurine concentration reaching 200-300 mg / kg, which corresponds to a single dose of the drug in terms of a person weighing 70 kg 14-20 g. It was believed that taurine acts through a system of secondary intermediaries, namely through cyclic nucleotides. It is known that this system is responsible for the rapid responses of cells to the action of certain hormones. On an isolated perfused heart, the potentiating effect of taurine on the sugar-lowering effect of insulin with an amino acid concentration in the experiment of 10 mM was revealed. A similar effect may be due to an increase in the activity of glycogen synthetase 1 and a decrease in the activity of phosphorylase. An insulin receptor was isolated and the order of affinity of taurine for this receptor was shown, as well as a suggestion was made about the possible effect of this acid through insulin receptors. However, these data do not give reason to recommend taurine for the treatment of patients with diabetes mellitus. Doses that can be applied from the above sources on the proposed mechanisms of action are too high. With absolute non-toxicity of taurine, but with prolonged use in a clinic in such concentrations, side effects may occur.

 It is known that when destabilizing diabetes mellitus, the composition of membrane phospholipids and the ratio of membrane cholesterol to phospholipids are violated. Currently, it is suggested that these changes can cause a deep metabolic disturbance in the cell. Indeed, in the treatment of patients with diabetes mellitus with drugs that can stabilize the course of the disease, there is a change in the ratio of phospholipids and, in the first place, the ratio of the main phospholipid of the inner membrane of phosphatidylethanolamine to the phospholipid of the outer membrane of phosphatidylcholine. Studies show: diet therapy preserves pathological changes in the ratio of phospholipids (FL). Diabeton normalizes the PL status of membranes in patients with newly diagnosed diabetes mellitus and does not affect long-standing forms. Biguanides correct cholesterol, but do not affect phospholipid disorders. Maninil (the main drug currently for type 2 diabetics) does not restore the lipid composition of the red blood cell and can aggravate shifts.

 The inventive taurine is proposed as a membrane stabilizer.

 It was suggested that taurine with prolonged use in small doses should change the phospholipid composition of the membrane and lipid metabolism, after which the course of the disease should stabilize. Indeed, the effect occurred approximately two weeks after the start of treatment. The accumulation of the drug in the body is excluded, since from already published works it is known that taurine, not accumulating in the tissues, is excreted with cholic acids and urine. It is almost impossible to shift the concentration of endogenous taurine, even with prolonged use in large doses.

 The doses used to treat patients with diabetes mellitus do not have a hypoglycemic effect, and in previous publications, experimenters did not work with a similar concentration of taurine on the whole animal, and moreover did not suggest a similar effect of taurine on the membrane neither in experimental diabetes mellitus, nor even in clinical conditions. It has been shown for the first time that with prolonged use of small doses of taurine in a clinic for patients with both types of diabetes, the normal phospholipid composition of red blood cells is restored, as well as the ratio of cholesterol to phospholipids. In the blood, the level of triglycerides decreases. Stabilization of the disease and, in some cases, a decrease in blood sugar was a consequence of membrane changes and, accordingly, carbohydrate metabolism.

 Selected doses for treatment were 0.5 g twice daily for the first month. In the future, as shown by experience, a dose of 0.25 g twice a day was sufficient with interruptions of one to two weeks. Patients who perfectly went on taurine did not even follow a strict carbohydrate diet.

 Clinical data.

 Under observation were 20 patients suffering from diabetes. Of these, two groups were formed: the 1st group of 10 people (5 men and 5 women), patients with diabetes mellitus of the insulin-dependent type (Type I): the 2nd group of 10 people (6 men, 4 women) with diabetes mellitus of the non-insulin-dependent type ( II type). The average age of patients of the 1st group was 27 + 1.9 years, the duration of the disease in this group of patients ranged from 0.5 to 16 years. All patients in this group received insulin therapy in two or three times, the average daily dose of which was 0.65 + 0.03 u / kg body weight. The course of diabetes in 4 cases was severe; patients had diabetic vascular complications (diabetic nephropathy, retinopathy) in the proliferative stage. The remaining 6 people suffered from moderate diabetes.

 The second group included patients with newly diagnosed diabetes mellitus who had not previously received any hypoglycemic therapy. The average age of patients in this group was 52 + 4.2 years. The course of diabetes in this group of patients was moderate, since it was not possible to achieve ideal compensation against the background of diet therapy. However, no pronounced diabetic vascular complications were observed in the 2nd group of patients, although age-related manifestations of atherosclerotic lesions were observed in 8 patients of this group, which was manifested by coronary heart disease and arterial hypertension.

 In order to study the clinical effect of taurine, patients of the 1st group received the pharmacopoeial drug taufon in a state of clinical compensation against the background of insulin therapy. In endocrinology, the concept of clinical compensation includes the following criteria: glycemia from 8 to 11 mmol / l; aglucosuria 5-10% of the sugar value of food. During the month of observation, no side effects, allergic reactions, or changes in the clinical analysis of blood, urine, or biochemical parameters were revealed. 8-10 days after the start of taufon therapy, patients noted the appearance of hypoglycemic conditions, which was forced to reduce the dose of insulin administered. After adjusting the daily dose of insulin, stabilization of diabetes mellitus was noted, which was manifested by a significant decrease in daily average glycemia (10.55 ± 0.39 mmol / L before treatment, 8.03 ± 0.04 mmol / L after therapy; p <<0.001) and the amplitude of glycemic fluctuations (from 3.79 ± 0.48 to 2.81 ± 0.026 mmol / L; p <0.05). There was no significant decrease in the average daily dose of insulin, although the average daily dose was reduced by 4-6 units. It should be noted that despite a decrease in the dose of insulin while taking taufon in 50% of cases, perfect compensation for diabetes mellitus was achieved, which was manifested by normoglycemia and aglucosuria (glucosuria before therapy 41.08 ± 5.79 g / day and after treatment 8.54 ± 2.73 g / day), which is an extremely difficult task in the treatment of patients suffering from type I diabetes. Against the background of admission, patients noted an improvement in general condition, a decrease in weakness, pain in the lower extremities.

 The observation of patients of the second group showed a significant decrease in daily average glycemia (from 10.69 ± 0.58 to 8.01 ± 0.6 mmol / L; p <0.01) and the amplitude of glycemic fluctuations (from 5.16 ± 0.088 to 3, 72 ± 0.81 mmol / L; p <0.05). At the same time, only two patients achieved perfect compensation for diabetes mellitus, which can be regarded as an “excellent” hypoglycemic effect. Thus, the effectiveness of taurine in type II diabetes is somewhat lower.

 Research results. Data on the membrane-stabilizing effect of taurine in diabetes mellitus.

 1. Change in the phosphalipid composition of the membrane of human red blood cells.

 As the main criterion, we took changes in the ratio of phosphatidylethanolamine (PE) to phosphatidylcholine (FC) of the main phospholipids characteristic of the inner and outer bilayer of the cell membrane. The content of all determined phospholipids of phosphatidylcholine, phosphatidylserine, sphingomyelin, lysophosphatidylcholine and phosphatidylethanolamine was taken as 100% and the percentage of each was calculated.

 The data are given in table. 1.

 The average ratio of PE: PX for healthy patients is 1: 1.

 Static processing showed that the difference between the numbers characterizing the PE: PF before and after treatment was significant p <0.01.

 2. An important characteristic of sarcolemma is the ratio of cholesterol (x) to phospholipids (PL). This ratio characterizes the rigidity of the membrane, from which the activity of a number of membrane enzymes follows.

 The data are given in table. 2.

 In control (in healthy people), the ratio ranges from 0.7 to 1.5.

 Thus, a month after treatment with taurine, a significant change (p <0.05) was observed only for triglycerides.

 Data on changes in the concentration of triglycerides of total cholesterol, cholesterol of high density lipoproteins and low density lipoproteins in the blood of patients with diabetes mellitus are given in table. 3.

 Significant significant changes in the treatment of taurine were also detected at the level of the cell membrane, which determines the clinical effect of the drug.

 Conclusion: the alleged membrane effects of small doses of taurine were confirmed during long-term treatment of patients with diabetes mellitus. For the first time after such treatment, objective data were obtained on improving the condition and stabilizing the course of the disease in patients with diabetes of both the first and second types.

Claims (1)

 The use of taurine as a membrane stabilizing agent for the treatment of patients with insulin-dependent and non-insulin-dependent diabetes mellitus.

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