RU2400245C1 - Preparation for controlling glycemia level and prevention of vascular complications in patients with disorders of carbohydrate metabolism and type 2 diabetes mellitus - Google Patents

Abstract

FIELD: medicine. ^ SUBSTANCE: invention relates to chemical-pharmacological industry, namely to creation of preparation for controlling glycemia level and prevention of vascular complications in patients with disorders of carbohydrate metabolism and type 2 diabetes mellitus. As said preparation, applied is BAA to food "Carb blocker Phase2/Phasa2«". ^ EFFECT: preparation has good tolerance and does not have side effects, allows prevention or considerably slow down of development of vascular complications at reaching state of compensation/subcompensation of carbohydrate metabolism. ^ 4 tbl, 1 dwg

Description

The invention relates to the chemical and pharmaceutical industry, namely, to the creation of herbal products for the prevention of hyperglycemia and additional glycemic control in patients with impaired carbohydrate metabolism, including patients with metabolic syndrome and impaired tolerance to carbohydrates and type 2 diabetes .

Diabetes mellitus (DM) is a serious medical and social problem, due to the significant prevalence of the disease, a steady increase in the number of patients, the high frequency, severity and progression of vascular complications, leading to early disability and high mortality. According to the International Diabetes Federation [1], currently there are 246 million patients with diabetes aged 20-79 years in the world, of which 85-95% are patients with type 2 diabetes. It is estimated that by 2030 the total number of patients with diabetes will increase to 366 million people [2].

It is generally recognized that chronic hyperglycemia is one of the leading causes of the development and progression of vascular complications of type 2 diabetes, such as macroangiopathies (peripheral angiopathy, coronary heart disease, atherosclerotic cardiosclerosis, heart failure, cerebrovascular disease, persistent arterial hypertension, leading to the development of myocardial infarction and myocardial infarction and which in the structure of mortality of patients is 70% [3, 4]), and microangiopathy (diabetic polyneuropathy, diabetic foot syndrome, retinopathy and nephropus tiya). Until recently, fasting glucose and glycated hemoglobin levels were considered as the main indicators of the quality of compensation for carbohydrate metabolism in patients with type 1 and 2 diabetes. However, in recent years, evidence has been obtained that indicates that no less importance is achieved in achieving optimal glycemic control and reducing the risk of developing late diabetic complications has post-food (postprandial) glycemia [5], associated with an increased risk of retinopathy and an increase in the thickness of the intima-media of the carotid artery, which is the beginning nym sign of atherosclerosis. In this regard, when assessing the results of treatment of type 2 diabetes, it is important not only to control the level of fasting blood glucose and glycated hemoglobin, but also to take into account the dynamics of post-food (postprandial) glycemia, which is an independent risk factor for the development of complications of this disease. Table 1 shows the following glycemic levels in capillary blood according to WHO recommendations for the stage of compensation / subcompensation.

Table 1 Indicators Compensation Subcompensation HbA1c (%) <7.0 7.1-7.5 Self-monitoring of glucose in capillary blood, mmol / l (mg%) Fasting Glycemia 5.0-6.0 6.1-6.5 (90-109) (110-120) Postprandial glycemia (2 hours after eating) 7.5-8.0 8.1-9.0 (136-144) (145-160) Glycemia before bedtime 6.0-7.0 7.1-7.5 (110-126) (127-135)

The main therapeutic goal in type 2 diabetes mellitus is the persistent achievement of compensation status values (including values of postprandial glycemia), which allows to slow down and / or avoid the development of diabetes complications (both macro- and microangiopathies).

Table 2 shows the data characterizing the dependence of the degree of risk of developing complications of diabetes mellitus on indicators of carbohydrate metabolism (European Diabetes Policy Group 1998-1999).

table 2 Indicator Low risk of angiopathy (target values) Risk of macroangiopathy Risk of microangiopathy HbAlc (%) ≤6.5 > 6.5 > 7.5 Fasting glycemia / before meals, mmol / l (mg%) in plasma of venous blood ≤6.0 (<110) > 6.0 (≥110) ≥7.0 (> 125) whole capillary blood (self-monitoring) ≤5.5 (<100) > 5.5 (≥100) > 6.0 (≥110) Postprandial glycemia (2 hours after eating), mmol / l (mg%) in venous blood plasma and in whole capillary blood (self-monitoring) <7.5 (<135) ≥ 7.5 (≥135) > 9.0

The basis of nutrition (for overweight - low-calorie - ≤1800 kcal / day) patients with impaired carbohydrate metabolism and patients with diabetes should be difficult to digest carbohydrates: 45-65% of the daily diet (the proportion of fat is 25-35%) (of which are saturated less than 10%), proteins - 15-20%). It is also necessary to limit easily digestible carbohydrates and include foods rich in plant fibers in the diet [14].

As you know, carbohydrate-containing products cause a different post-food glycemic reaction, which depends not only on the quantity and quality of carbohydrates in the product, but also on biologically active substances contained in food, which have inhibitory activity against a number of digestive enzymes, including alpha-amylase [ 6-8].

Alpha amylase inhibitors isolated from wheat germ, as shown in vitro, reduce the rate of digestion of starch, and their addition to starch-containing food reduces its post-food glycemic effect [7, 9]. It was found that the use of a pancreatic alpha-amylase inhibitor isolated from white bean beans (Phasaolus vulgaris) was accompanied by a decrease in glycemic indices in experimental animals, including type 2 diabetes [7, 10]. Studies on healthy volunteers showed a decrease in the area under the glycemic curve when consuming foods rich in complex carbohydrates, including 1.5 g of Phase 2 bean extract [11]. Along with this, a greater decrease in body weight, waist and hips was found, combined with a decrease in blood triglycerides in overweight individuals who received white bean bean extract, standardized for alpha amylase inhibition activity [12, 13].

The dietary supplement “Phase 2 / Phasa 2® Calorie Blocker”, developed by the DIOD Plant of Environmental Engineering and Ecological Nutrition, is a 0.44 g tablet containing Phase 2 / Phasa 2® substance (bean seed extract - 250 mg) and auxiliary components (fibregam).

The objective of the present invention is the use of "Phase 2 / Phasa 2® Calorie Blocker" as a means for controlling glycemia and for preventing vascular complications in patients with impaired carbohydrate metabolism (including impaired tolerance to carbohydrates, metabolic syndrome) and diabetes type 2.

In a clinical trial, the dynamics of postprandial glycemia in patients with type 2 diabetes after a standard carbohydrate load (wheat bread, 50 g of carbohydrates) and the same load with the inclusion of 2 dietary supplement tablets “Phase 2 / Phasa 2® Calorie Blocker” was evaluated.

The study was carried out under controlled conditions of a hospital on the basis of the Department of Metabolic Diseases, State Research Institute of Nutrition RAMS.

The study was conducted on 15 patients with type 2 diabetes, women and men, aged 40 to 69 years, who are in the stage of subcompensation of carbohydrate metabolism, without insulin requirements, on standard diet therapy, having concomitant diseases that do not require intensive pharmacotherapy.

The criteria for inclusion in the study were:

type 2 diabetes mellitus;

age of patients from 40 to 69 years;

metabolic subcompensation;

the absence of acute diseases of the gastrointestinal tract and other acute conditions,

the patient's ability to adequately collaborate in the research process;

patient informed consent.

Exclusion criteria from the study were:

type 1 diabetes mellitus;

less than 40 years old and over 69 years old;

metabolic decompensation;

insulin demand;

acute or exacerbation of chronic diseases of the gastrointestinal tract and other acute diseases.

Table 3 shows the clinical characteristics of patients with type 2 diabetes who participated in the study.

Table 3 Indicator M ± m Age years 55.3 ± 2.1 Duration of the disease, years 3.9 ± 0.8 Body weight 104.3 ± 5.1 Body mass index, kg / m ² 38.3 ± 1.8 Blood pressure, mmHg systolic 133.8 ± 3.7 diastolic 85.4 ± 1.8 Glycemia, mmol / l deoxygenated blood 8.3 ± 0.5 capillary blood 7.0 ± 0.4

All patients had obesity I-III degree. The average body mass index in the group was 38.3 ± 1.8 kg / m ² . At the time of the initial examination, the stage of metabolic subcompensation was determined in all patients: the level of basal glycemia in venous blood in the group averaged 8.3 ± 0.5 mmol / L, in capillary blood - 7.0 ± 0.4 mmol / L.

All patients were previously informed about the research procedure, about the rules of behavior in the research process, informed consent was received from all patients to participate in the study.

Each patient was tested twice, with an interval of one week, on a fasting glucose level in capillary blood (after 14-hour fasting) and 30, 60, 120 and 180 minutes after a standard carbohydrate load (wheat bread, 50 g of carbohydrates) load with the inclusion of 2 tablets of dietary supplements for food "Calorie Blocker Phase 2 / Phasa 2®" - with a weekly interval. Blood was drawn from the finger using disposable lancets. Glycemia was determined using a One Touch® Ultra ™ meter.

In the group of subjects, the entire volume of research was completely completed; there were no refusals to continue research. During the study, patients did not take oral hypoglycemic and other drugs.

The calculation of the areas under the glycemic curves obtained in the course of this study was carried out according to the generally accepted method using the following formulas:

[(A + B / 2) × t] + [(B + C) × T / 2] or [(A + B / 2) × t] + [(B + C) × T / 2] + [( С + D) × Т / 2] - if the last glycemic point (120 and 180 min) was located above the basal level;

[(A + B / 2) × t] + (B ² × T) / [2 × (B + C)] or [(A + B / 2) × t] + [(B + C) × T / 2] + (C ² × T) / [2 × (C + D)] - if the last glycemic point (120 and 180 min) was below the basal level.

A, B, C, D - an increase in blood glucose, i.e. the difference between its basal level and content at the studied time intervals (t, T).

Based on the obtained data, the glycemic index (GI) of wheat bread was calculated with the inclusion of 2 dietary supplement tablets for food “Phase 2 / Phasa 2® Calorie Blocker”.

The obtained research results were processed statistically on a PC using the SPSS 11.5 application package for Windows. The results are presented as mean values and their standard error (M ± m). The significance of differences in the average values was assessed using Student's t-test.

All patients tolerated inclusion of dietary supplements in the standard carbohydrate load to food “Phase 2 / Phasa 2® Calorie Blocker”, no side effects were noted during the study.

The results of the study of post-food glycemia in patients with type 2 diabetes after consuming wheat bread with the inclusion of dietary supplement “Phase 2 / Phasa 2® Calorie Blocker” and standard carbohydrate load (wheat bread, 50 g carbohydrates) are presented in Table 4.

Table 4 Time intervals The level of glycemia, mmol / l wheat bread with the inclusion of dietary supplement for food "Phase2 / Phasa 2® calorie blocker" wheat bread (control) On an empty stomach 6.63 ± 0.24 6.60 ± 0.30 30 minutes after exercise 9.10 ± 0.31 9.33 ± 0.54 % of baseline 37.8 40.9 60 min after exercise 11.0 ± 0.42 11.94 ± 0.96 % of initial level 66.7 80.3 120 min after exercise 9.03 ± 0.87 9.12 ± 0.84 % of baseline 36,4 37.9 180 min after exercise 6.58 ± 0.37 6.93 ± 0.55 % of baseline -0.75 4,5

Change in post-food glycemia (in% of the initial level) in patients with type 2 diabetes after consuming wheat bread with the inclusion of dietary supplement “Phase 2 / Phasa 2® calorie blocker” and only wheat bread (control) is shown in the drawing, where 1 is wheat bread with the inclusion of dietary supplement for food "Calorie Blocker Phase 2 / Phasa 2®", 2 - wheat bread (control)

From table 4 and the drawing it can be seen that the inclusion of 2 tablets of dietary supplements for food “Phase 2 / Phasa 2® Calorie Blocker” in the standard carbohydrate load of wheat bread (50 g of carbohydrates) was accompanied by a lower increase in glucose in capillary blood after 30 and 60 minutes after exercise, compared with an increase in glycemia after eating only wheat bread at the same time intervals.

When consuming wheat bread with the inclusion of dietary supplement for food “Phase 2 / Phasa 2® Calorie Blocker”, the level of post-food glycemia 180 minutes after loading decreased to the initial values, and after the standard carbohydrate load of wheat bread, it was 4.5% higher than the initial one.

Comparative assessment of the areas under glycemic curves in observed patients with type 2 diabetes after consuming wheat bread with 2 tablets of dietary supplements for food “Phase 2 / Phasa 2® calorie blocker” (drawing, curve 1) and standard carbohydrate load (wheat bread, 50 g of carbohydrates, drawing, curve 2) showed that the area under the glycemic curve after consuming wheat bread with 2 tablets of dietary supplements for food “Calorie Blocker Phase 2 / Phasa 2®” was significantly less than when consuming wheat bread (430, 3 ± 61.3 mmol / L × min vs. 576.2 ± 78.9 mmol / L × m n, p <0,05). Based on the obtained data, the GI of wheat bread was calculated with the inclusion of 2 dietary supplement tablets for food “Phase 2 / Phasa 2® Calorie Blocker”, which amounted to 74.7%.

Thus, the consumption by patients of type 2 diabetes of dietary supplements to food “Phase 2 / Phasa 2® calorie blocker” is accompanied by a tendency to a decrease in post-food glycemia 30 and 60 min after a carbohydrate load and a statistically significant decrease in the area under the glycemic curve in observed patients when this dietary supplement into a standard carbohydrate load of wheat bread.

The study showed good tolerance to dietary supplement “Phase 2 / Phasa 2® Calorie Blocker” in the amount of 2 tablets (500 mg of bean seed extract): no adverse events and adverse reactions were observed in the observed patients with type 2 diabetes.

Evaluation of the postprandial glycemic reaction in patients with type 2 diabetes revealed a smaller area under the glycemic curve when they include the Phase 2 / Phasa 2® Calorie Blocker dietary supplement in a standard carbohydrate load compared to a standard carbohydrate load (wheat bread, 50 g carbohydrates).

List of references

1. Diabetes Atlas. Executive Summary. Third edition / International Diabetes Federation. - Brussel, 2006.

2. Wild S., Roglic G., Green A. et al. Global prevalence of diabetes. Estimates for the 2000 and projections for 2030 // Diabetes Care. - 2004 .-- Vol. 27. - P.1047-1053.

3. Laakso M. Hyperglycaemia and cardiovascular disease in type 2 diabetes // Diabetes. - 1999. - Vol. 48. - P.937-942.

4. Niskanen L., Turpeinen A., Penttila I., Uusitupa M.I. Hyperglycemia and compositional lipoprotein abnormalities as predictors of cardiovascular mortality in type 2 diabetes: a 15-year follow-up from the time of diagnosis // Diabetes Care. - 1998 .-- Vol.21. - P. 1861-1869.

5. Ametov A.C., Miller A.B. Management of diabetes mellitus: the role of postprandial hyperglycemia and the possibility of its correction // BC. - 2007. - T.15. - No. 27 (308). - S.2053-2058.

6. Golay A., Schneider H., Temler E., Felber J.P. Effect of trestatin, an amylase inhibitor, incorporated into bread, on glycemic responses in normal and diabetic patients // Am.J. Clin. Nutr. - 1991. - Vol. 53. - P.61-65.

7. Jenkins DJA, Wolever TMS, Jenkins AL Diet factors affecting nutrient absorption and metabolism // Modern nutrition in health and disease. 8 ^th ed. / Ed. MEShils, JAOlson, M.Shike. - 1994 .-- P.583-602.

8. Tormo M.A., Gil-Exojo I., Romero de Tejada A., Campillo J.E. Hypoglycaemic and anorexigenic activities of an alpha-amylase inhibitor from white kidney beans (Phasaolus vulgaris) in Wistar rats // Br. J. Nutr. - 2004 .-- Vol.92. - P.785-790.

9. Puis W., Keup U. Influence of an amylase inhibitor (BAY d 7791) on blood glucose, serum insulin and NEFA in starch loading test in rats, dogs and man // Diabetologia. - 1973. - Vol. 9. - P.97-101.

10. Tormo M.A. Gil-Exojo I., Romero de Tejada A., Campillo J.E. White bean amylase inhibitor administered orally reduces glycaemia in type 2 diabetic rats // Br. J. Nutr. - 2006. - Vol. 96. - P.539-544.

11. Vinson J.A. Investigation of the Efficacy of Phasa 2® a Purified Bean Extract from Pharmachem Laboratories // http://www.phase2info.com/clin_studies/study inveseffici.asp.

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13. Udani J., Singh B. B. Blocking carbohydrate absorption and weight loss: a clinical trial using a proprietary fractionated white bean extract // Altern. Ther. Health Med. - 2007. - Vol.13. - P.32-37.

14. Algorithms for specialized medical care for patients with diabetes. Ed. I.I.Dedova, M.V. Shestakova. 2nd Edition. Moscow, 2006

Claims (1)

The use of dietary supplement “Calorie Blocker Phase 2 / Phasa 2®” as a means of glycemic control and prevention of vascular complications in patients with impaired carbohydrate metabolism and type 2 diabetes.

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