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Effect of vitamin-mineral complex ALFAVIT Diabetes on manifestations of diabetic polyneuropathy in patients with diabetes undergoing complex therapy

Authors:Chernikova NA, Ametov AS, Voychik EA, Rogova LA
Location:Department of Endocrinology and Diabetology of Academy of Postgraduate Education

One of the most frequent complications of diabetes mellitus (DM) is diabetic polyneuropathy, which leads to reduced quality of life and disability [1]. If the duration of diabetes is more than 20 years, diabetic polyneuropathy is found in more than 50% of the patients [9]. Prevalence of this complication among patients with diabetes ranges from 28 to 60% and depends on the studied sample and methods of diagnosis [5]. Despite the great recent advances in the understanding of the peripheral nerve lesions pathogenesis in diabetes, so far there is single no highly efficient method of treatment of diabetic polyneuropathy.

Modern therapy of diabetic polyneuropathy

1. Diabetes compensation

Hyperglycemia starts a cascade of vascular and metabolic disorders that cause the development of late complications of diabetes, including diabetic polyneuropathy. In this regard, the main objective is to achieve target glycemic levels. Long-term studies have shown that intensive therapy of diabetes and maintenance of glucose levels close to normoglycemia, significantly reduces the likelihood of polyneuropathy [4, 5]. The incidence of this complication is higher in patients with the traditional treatment of DM, compared with patients receiving intensive care. At the same time some patients, which received intensive care of diabetes also develop diabetic polyneuropathy. This indicates that even small and short-term fluctuations in blood sugar can lead to the development of this pathology, and stresses the need for additional therapy of diabetic polyneuropathy, including prophylaxis therapy.

Antioxidants

In recent years, oxidative stress is one of the most studied mechanisms of development of late vascular complications in diabetes [5, 6]. Oxidative stress and activation of lipid peroxidation, including low density lipoprotein, is accompanied by inhibition of endothelial nitric oxide (NO) synthesis and activation of nuclear factor kB (NF-kB), which causes release of substances that impair blood flow, such as endothelin-1 [ 4, 5]. Currently, the role of oxidative stress in the development of diabetic polyneuropathy is considered as one of the leading. Therefore, it is logical to use drugs with antioxidant effect. Elimination of oxidative stress in patients with diabetes and the use of antioxidants leads to increased levels of NO in serum, reduced severity of clinical symptoms caused by endothelial dysfunction. That is why a major focus of the treatment of diabetic polyneuropathy is given to administration of antioxidants such as vitamins C, E, A and lipoic acid. Alpha-Lipoic acid is used to treat diabetic neuropathy for few decades. Its efficacy is proven in numerous large-scale studies: ALADIN, DECAN, ALADIN II, ALADIN III [6, 7]. The positive effect of the drug on metabolism is carried out through several mechanisms: inhibition of glycosylation end-products formation, improvement of endoneural blood flow, restoration of pool of antioxidants in the body [5, 6]. Lipoic acid plays an important role in boosting cellular energy production, by participating in the mitochondrial electron transport chain (compensates NADH deficiency [6, 7]).

DM is characterized by decrease in blood and tissues levels of ascorbic acid and tocopherol, which are members of organism’s antioxidant defense system. In experimental models, the use of these vitamins reduced the manifestations of diabetic polyneuropathy, but conclusive data on their clinical efficacy to date has not been received. Therapy with B vitamins cannot be attributed directly to the pathogenetic therapy because reduction of vitamin content of this group was not shown in blood or tissues of diabetic patients, but they increase the neurotrophic nerve protection and the ability of nerves to regenerate. In addition, B-vitamins had proved their clinical efficacy in pain treatment diring diabetic polyneuropathy, and they are widely used for this purpose in some countries, including Russia, Germany and Japan. Several randomized, double-blind, placebo-controlled studies had proved the effectiveness of benfotiamine or its combinations with vitamin B 6 and B 12, which had shown a significant decrease in pain and paresthesias, lowering of vibration sensitivity threshold and improvement of EMG indices of the functional state of the nerve [8].


The clinical study of vitamin-mineral complex ALFAVIT Diabetes in 2008, in the Department of Endocrinology and Diabetology with the Course of Endocrine Surgery of Academy of Postgraduate Education on the basis of CDB № 1 RZhD. The goal of the study was to evaluate the influence of preparation on the manifestations of diabetic polyneuropathy in patients with diabetes mellitus type 1 and 2 receiving complex therapy.

Patients received one tablet (Table 1) of each color during the day with meals, in any sequence (the interval between pills was 4-6 hours). The drug was prescribed in addition to the ongoing complex glucose reduction-therapy (diet, insulin and / or oral hypoglycemic agents).

Composition of ALFAVIT Diabetes

Table 1

Component

Content, mg

Tablet № 1

Iron

15

B1

4

Vitamin C

50

B9

0.25

Succinic acid

50

Vitamin A

0.5

Copper

1

Lipoic acid

15

Bilberry extract (shoots)

30

Tablet № 2

Vitamin A

0.5

Vitamin C

50

Vitamin E

30

B2

3

B3

30

B6

3

Manganese

3

Selenium

0.07

Zinc

18

Magnesium

40

Iodine

0.15

Extract of burdock (burdock)

30

Dandelion extract

30

Tablet № 3

D3

0.005

K1

0.12

Biotin

0.07

B5 (calcium pantothenate)

7

B9

0.25

B12

0.004

Calcium

150

Chromium (picolinate)

0.15

The study was conducted as an open, controlled trial.

Duration of drug administration was 30 days, with medical examination of patients before the study (Week 0) and at the first, second, third and fourth weeks from the start of the study. All patients involved in the study signed an informed consent, were trained in the diabetes school and recieved an individual meal plan.

In accordance with the protocol, the study included 30 patients diagnosed with diabetes type 1 and 2 (15 patients with each type of diabetes), including 14 men and 16 women aged 21 to 65 years, with duration of diabetes of 15 years and HbA1c not greater than 10%.

The criteria for assessing the impact of the drug on carbohydrate metabolism were glucose blood levels after fasting and after meals, and HbA1c after the admission of test preparation.

The criteria for impact assessment of the drug on manifestations of diabetic neuropathy were changes in the indices of feet sensitivity tests, and alterations of EMG after intake of the studied preparation.

Methods

The control visits included comprehensive clinical examination of patients with measurement of weight, biochemical analysis of blood, HbA1c ,, measurement of glucose levels after fasting and 2 hours after meals.

Neurological testing of patients was conducted in the office of "Diabetic Foot" with the assesment of vibration, tactile, temperature and pain sensitivity. The conducting function of n. reroneus dxt and n. suralis dxt was measured using stimulation electromyography method. Since hyperthyroidism is an contraindication for preparation administration, all patients were investigated for TSH levels TSH prior to administration of vitamin-mineral complex,.

Statistical analysis of the results were carried out using variation statistics.

In addition, all side effects and changes of the medical therapy were recorded.


Results

General characteristics of studied patients are presented in the Table 2.

Table 2

Total number of patients, pers.

- Type 1 diabetes

- Type 2 diabetes

30 people (14 males and 16 females)

15 people

15 people

Age, years

43.87 + 14.17 years

Duration of diabetes, years

- Type 1 diabetes

- Type 2 diabetes

6,43 + 4,39 years

6.73 + 4.56

6.13 + 4.36

Body weight, kg

- Type 1 diabetes

- Type 2 diabetes

83.88 + 17.7

74.97 + 15.26

92.79 + 15.75

Late complications of diabetes

- Diabetic polyneuropathy

- Diabetic retinopathy I-II stages.

- Fatty hepatosis


14 people

14 people

1918 attendees

The level of TSH, IU / ml

1,96 + 0,92 (normal 0,4-4,0)

All patients included in the study recieved the drug for 30 days. All examined patients showed improvement of well-being, with good tolerability, no side effects and with no allergic reactions.

Effect on carbohydrate and lipid metabolism

All studied patients showed a trend to lowering of glucose after fasting, especially 2 hours after meals, and did not reveal negative dynamics in the change of HbA1c and lipid profile. The data is presented in Table 3.

Table 3

Investigated parameters

Before treatment

After 30 days of drug administration

Blood glucose, fasting, mmol/l

- Type 1 diabetes

- Type 2 diabetes

9.0 + 3.99

8.8 + 5.39

9.15 + 2.95

8.27 + 1.7

8.07 + 2.06

8.43 + 1.51

Blood glucose 2 hours after meals, mmol/l

- Type 1 diabetes

- Type 2 diabetes

9.3 + 3.12


8.85 + 4.48

9.89 + 1.89

8.24 + 2.40


7.68 + 2.97

8.88 + 1.98

HbA1c, %

- Type 1 diabetes

- Type 2 diabetes

7.91 + 1.22

7.71 + 1.16

8.09 + 1.27

7.95 + 1.71

8.17 + 1.78

7.64 + 1.65

Cholesterol, LDL, mmol/l

2.65 + 0.77

2.79 + 0.69

Triglycerides, mmol/l

2.16 + 1.66

1.73 + 1.01

Cholesterol-HDL, mmol/l

1.29 + 0.46

1.24 + 0.47

Effect on manifestations of diabetic polyneuropathy

All patients with clinical manifestations of diabetic neuropathy have shown a reduction of characteristic complaints, namely: numbness and burning sensations in the feet. Patients also demonstrated a moderate positive dynamics in electromyographic indicators: increase of amplitude of motor nerves M-response at 1.2, 3.0, 5.4 mV in 3 patients, of excitation propagation velocity in the tibia at 2 m/s in 2 patients, 3 m/s in 1 patient; increase in the amplitude response of sensory nerves at 0,9-1, 1-1,4 mV in 3 patients, of excitation propagation velocity at 2 m/s in 5 patients. The results of neurological examination are presented in Table 4.

Table 4

Investigated parameters

Before treatment

After 30 days of drug administration

EMG-study:

n. peroneus dxt

Amplitude of M-response, mV

Propagation of excitation (lower leg), m/s

Propagation of excitation (knee level), m/s

Residual latency, ms

n. suralis dxt

Аmplitude of М-response, mV

EOT, m / s



5.35 + 2.72

41.6 + 4.64

42.36 + 4.63

2.29 + 0.11

6.07 + 1.93

36.7 + 0.5



5.72 + 2.71

42.1 + 4.21

42.69 + 4.32

2.08 + 0.51

6.36 + 1.92

39.6 + 2.72

Pallesthesia

7-8 points in 14 patients

5-6 points in 11 patients

2-4 points in 5 patients

7-8 points in 15 patients

5-6 in 10 patients

2-4 points in 5 patients

Tactile sensitivity

Disrupted in 6 patients

Disrupted in 6 patients

Thermoesthesia

Disrupted in 14 patients

Disrupted in 14 patients

Algesthesia

Disrupted in 4 patients

Disrupted in 4 patients

Thus, our study showed that the use of vitamin-mineral complex in treatment of diabetes has a positive effect on the course of this diseases and is well tolerated in the absence of any adverse events. Patients who have undergone treatment had marked improvement in subjective well-being and mood.

According to the results of objective examination the preparation had no adverse effects on carbohydrate and lipid metabolism and did not cause weight gain.

Neurological examination of all patients with symptomatic diabetic polyneuropathy, had shown a positive dynamic, which makes it advisable to use this drug for prevention of diabetic polyneuropathy in patients with diabetes mellitus type 1 and 2.

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