AU2023201838B2 - Electrical stimulation system and a method thereof - Google Patents

Abstract

The present invention relates to an electrical stimulation system and a method thereof. The electrical stimulation system includes an electrical stimulation generator and at least one electrode structure. The electrical stimulation generator is used to generate an electric pulse combination which is transmitted to the skin of an individual through the electrode structure for stabilizing blood glucose fluctuations and reducing inflammation. 1000 3 2 2

Description

1000 3

2 2

ELECTRICAL STIMULATION SYSTEM AND A METHOD THEREOF BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to an electrical stimulation system and

a method thereof, particularly a system and method for generating

electrical pulse combinations and delivering the electrical pulse

combinations to the skin of a diabetic patient for stabilizing blood

glucose fluctuations or reducing inflammation.

2. Description of Related Art

Type 2 diabetes is a chronic metabolic disease, causing

hyperglycemia due to relative insulin deficiency, and insulin resistance.

No cure for type 2 diabetes has yet been developed. Drug therapy is still

the most common way to reduce hyperglycemia and diabetes

complications. However, taking oral antidiabetic drugs such as

biguanides, sulfonylureas, meglitinides, inhibitors or GLP-1 analogs

I may cause discomfort to patients (such as hypoglycemia) due to drug side effects, which may result in decreased quality of life and reluctance of patients to take their medications on time. Therefore, there is an urgent need for a non-drug technique that can assist or replace current treatments.

Furthermore, there are currently few relevant data on the

application of Transcutaneous Electrical Nerve Stimulator (TENS) to the

human body to treat or improve diabetic diseases. Only a few documents

in the prior art disclosed that the use of electrical stimulation devices can

reduce the glycated hemoglobin (HbAlc) and fasting plasma glucose

levels in diabetes-induced model mice, but there is no such effect as

effectively stabilizing blood glucose fluctuations and reducing related

inflammation in humans.

Accordingly, to solve the problem that the prior art and the

conventional electrical stimulation device cannot be effectively applied

to the human body to treat type 2 diabetes and etc., the present invention

provides an electrical stimulation system that can generate electric pulse combinations and transmit electric pulse combinations to the skin of individuals through the electrode structure. Above all, it can effectively stabilize blood glucose fluctuations in diabetic patients and reduce the expression of inflammatory factors in their bodies.

SUMMARY OF THE INVENTION

The present invention is to provide an electrical stimulation system

and a method for generating electric pulse combinations, whereby the

generated electric pulse combination can improve diabetes-related

diseases. Moreover, the electrical stimulation system of the present

invention generates an electric pulse combination, which is transmitted

to the body through the electrode structure attached to the skin of human

body. The electrical stimulation system of the present invention is a

non-invasive and portable electrical stimulation system that not only has

no risk of side effects but is also more suitable than current diabetes

medications when used on the human body. Therefore, the electric pulse combinations generated by the electrical stimulation system is capable of stabilizing blood glucose fluctuations and reducing inflammation in diabetic patients.

To achieve the purpose described above, the present invention

provides an electrical stimulation system including an electrical

stimulation generator and at least one electrode structure. The electrical

stimulation generator is to generate an electric pulse combination,

wherein a frequency of the electric pulse combination ranging from 1 to

20,000 Hz, and comprises a first frequency group, a second frequency

group, and a third frequency group, wherein the first frequency group,

the second frequency group, and the third frequency group are

respectively composed of multiple single-phase pulse groups, wherein

each single-phase pulse group has a duty cycle greater than or equal to

50% and a waveform that is a square wave. The electrode structure is

electrically connected to the electrical stimulation generator and having

a contact surface applied to the skin of an individual to deliver the

electric pulse combination; wherein the electric pulse combination is outputted in sequence from the first frequency group to the third frequency group, wherein the first frequency group ranges from 10 to

20,000 Hz, the second frequency group ranges from 1 to 30 Hz, and the

third frequency group ranges from 5 to 30 Hz.

In one aspect of the present invention, there is provided an electrical

stimulation system, comprising:

an electrical stimulation generator used to generate an electric

pulse combination, wherein a frequency of the electric pulse

combination ranging from 1 to 20,000 Hz, and comprises a first

frequency group, a second frequency group, and a third frequency group,

wherein the first frequency group, the second frequency group, and the

third frequency group are respectively composed of multiple

single-phase pulse groups, wherein each single-phase pulse group has a

duty cycle greater than or equal to 50% and a waveform that is a square

wave;

at least one electrode structure electrically connected to the

electrical stimulation generator and having a contact surface applied to the skin of an individual to deliver the electric pulse combination; wherein the electric pulse combination is outputted in sequence from the first frequency group to the third frequency group, wherein the first frequency group ranges from 10 to 20,000 Hz, sequentially includes the first single-phase pulse group of 18,122 Hz, the second single-phase pulse group of 10,000 Hz, the third single-phase pulse group of 7,344

Hz, the fourth single-phase pulse group of 5,000 Hz, the fifth

single-phase pulse group of 4,200 Hz, the sixth single-phase pulse group

of 3,672 Hz, the seventh single-phase pulse group of 3,175 Hz, the

eighth single-phase pulse group of 3,000 Hz, the ninth single-phase

pulse group of 2,127 Hz, the tenth single-phase pulse group of 2,112 Hz,

the eleventh single-phase pulse group of 2,007 Hz, the twelfth

single-phase pulse group of 1,865 Hz, the thirteenth single-phase pulse

group of 1,850 Hz, the fourteenth single-phase pulse group of 1,550 Hz,

the fifteenth single-phase pulse group of 1,234 Hz, the sixteenth

single-phase pulse group of 1,043 Hz, the seventeenth single-phase

pulse group of 1,000 Hz, the eighteenth single-phase pulse group of 921

Hz, the nineteenth single-phase pulse group of 880 Hz, the twentieth

single-phase pulse group of 867 Hz, the twenty-first single-phase pulse

group of 807 Hz, the twenty-second single-phase pulse group of 778 Hz,

the twenty-third single-phase pulse group of 751 Hz, the twenty-fourth

single-phase pulse group of 730 Hz, the twenty-fifth single-phase pulse

group of 705 Hz, the twenty-sixth single-phase pulse group of 668 Hz,

the twenty-seventh single-phase pulse group of 652 Hz, the

twenty-eighth single-phase pulse group of 625 Hz, the twenty-ninth

single-phase pulse group of 612 Hz, the thirtieth single-phase pulse

group of 595 Hz, the thirty-first single-phase pulse group of 542 Hz, the

thirty-second single-phase pulse group of 522 Hz, the thirty-third

single-phase pulse group of 484 Hz, the thirty-fourth single-phase pulse

group of 462 Hz, the thirty-fifth single-phase pulse group of 435 Hz, the

thirty-sixth single-phase pulse group of 421 Hz, the thirty-seventh

single-phase pulse group of 380 Hz, the thirty-eighth single-phase pulse

group of 348 Hz, the thirty-ninth single-phase pulse group of 302 Hz, the

fortieth single-phase pulse group of 160 Hz, the forty-first single-phase pulse group of 141 Hz, the forty-second single-phase pulse group of 125

Hz, the forty-third single-phase pulse group of 95 Hz, the forty-fourth

single-phase pulse group of 80 Hz, the forty-fifth single-phase pulse

group of 66 Hz, the forty-sixth single-phase pulse group of 40 Hz, and

the forty-seventh single-phase pulse group of 13 Hz, the output time of

the first frequency group is between 2300 and 2350 seconds, the second

frequency group ranges from 1 to 30 Hz, sequentially includes the

forty-eighth single-phase pulse group of 9 Hz, the forty-ninth

single-phase pulse group of 6 Hz, the fiftieth single-phase pulse group of

1 Hz, the fifty-first single-phase pulse group of 28 Hz, the fifty-second

single-phase pulse group of 19 Hz, the fifty-third single-phase pulse

group of 10 Hz, the fifty-fourth single-phase pulse group of 8 Hz, the

fifty-fifth single-phase pulse group of 6 Hz, and the fifty-sixth

single-phase pulse group of 5 Hz, the output time of the second

frequency group is between 900 and 1000 seconds, and the third

frequency group ranges from 5 to 30 Hz, sequentially includes the

fifty-seventh single-phase pulse group of 6 Hz, the fifty-eighth single-phase pulse group of 7 Hz, the fifty-ninth single-phase pulse group of 8 Hz, the sixtieth single-phase pulse group of 17 Hz, and the sixty-first single-phase pulse group of 26 Hz, the output time of the third frequency group is between 320 and 400 seconds.

In one embodiment, the output time of the first frequency group is

between 2300 and 2350 seconds, the output time of the second frequency

group is between 900 and 1000 seconds, and the output time of the third

frequency group is between 320 and 400 seconds.

In one embodiment, the output time of the electric pulse

combination is between 3520 and 3750 seconds.

In one embodiment, the electric pulse combination has a potential

difference, which is less than 10Vpp.

In one embodiment, the electrode structure contacts the abdominal

skin of the individual.

In one embodiment, the electrical stimulation system is capable of

improving symptoms of diabetes, which includes stabilizing blood

glucose fluctuations or reducing inflammation.

In one embodiment, stabilizing blood glucose fluctuations refers to

reducing glycemic variability (GV).

In one embodiment, reducing inflammation refers to decreasing

the protein expression of C-reactive protein (CRP) and fibroblast growth

factor 21 (FGF-21), which also has the potential to reduce fibrosis.

The present invention further provides a method for generating an

electric pulse combination in the electrical stimulation system, and the

electric pulse combination generated by the method will be delivered to

a diabetic patient through an electrode structure. By transdermally

delivering a single-phase pulse combination generated by this method to

an individual, it can effectively reduce the expression of inflammatory

factors and stabilize blood glucose fluctuation in the body of diabetic

patients, which shows better efficacy than the prior art.

To achieve the purpose described above, the present invention

provides an electrical stimulation system and a method that generates the

electric pulse combination.

After referring to the drawings and the implementation methods described later, those with ordinary knowledge in this field can understand other objectives of the present invention, as well as the technical means and implementation modes of the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic view of the electrical stimulation system of

the present invention;

FIG. 2 is a graph of the mean amplitude of glycemic excursion

(MAGE) of diabetic patients after using the electrical stimulation system

in one embodiment of the present invention;

FIG. 3 is a graph of the mean amplitude of glycemic excursion

(MAGE) of diabetic patients in different groups after using the electrical

stimulation system in one embodiment of the present invention;

FIG. 4 is a graph of the inflammatory factor C-reactive protein

(CRP) of the diabetic patients after applying the electrical stimulation

system in one embodiment of the present invention;

FIG. 5 is a graph of the inflammatory factor fibroblast growth

factor 21 (FGF-21) of the diabetic patients after applying the electrical

stimulation system in one embodiment of the present invention;

FIG. 6 is a plot of the electric pulse combination of one

embodiment of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

Reference will now be made in detail to the embodiments of the

present invention, examples of which are illustrated in the

accompanying drawings, and are not intended to limit the present

invention, applications, or implementations described in these

embodiments. Wherever possible, the same reference numbers are used

in the drawings and the description to refer to the same or like parts. It

should be noticed that, in the following embodiments and the attached

drawings, elements unrelated to the present invention are omitted from the depiction; and dimensional relationships among individual elements in the drawings are provided only for ease of understanding, but not to limit the actual scale.

Please refer to FIG. 1, which is a specific schematic diagram of an

electrical stimulation system 1000 according to one embodiment of the

present invention. The electrical stimulation system 1000 includes an

electrical stimulation generator 1 and two electrode structures 2. The

electrical stimulation generator 1 can be connected to the electrode

structures 2 through a signal transmission line. The electrode structures 2

are attached to an individual's abdomen and can deliver an electric pulse

combination generated by the electrical stimulation generator 1 to the

individual. It should be noted that the use of the signal transmission line

and the corresponding electrode structures 2 in the electrical stimulation

system 1000 in this embodiment is an illustration, which can be adjusted

according to the usage scenario or requirement and is not limited to this

embodiment.

In this embodiment, the electrical stimulation system 1000 can include an interface module 3. The main function of the interface module

3, which is not particularly limited in the present invention, is to allow

users to operate and adjust the electrical stimulation system 1000. The

interface module 3 includes the system operation switch and the

command signal for the default program execution, and to display the

operation information for users.

The electrical stimulation generator 1 is used to generate an

electric pulse combination, and the electrical stimulation pulse

combination includes a first frequency group, a second frequency group,

and a third frequency group. The first frequency group, the second

frequency group, and the third frequency group are respectively

composed of a plurality of single-phase pulse groups, the single-phase

pulse group has a duty cycle greater than or equal to 50%, and a

waveform as a square wave.

The electrical stimulation generator 1 can include a control

module, a driving module, and an output module (not shown in the

figure), the combination of the aforementioned modules can trigger and receive the command signal generated by the interface module 3 and then can output the corresponding driving signal to adjust and output the preset electric pulse with relevant duty cycle, frequency and potential difference in the program. It should be noted that the combination of the control module, the driving module, and the output module can be adjusted according to actual needs, which is not limited to the present invention.

In this embodiment, the electrode structures 2 are sheet-like,

cloth-like or wearable device structure, which can be pasted or contact

the individual, and the electrode structures 2 are electrically connected to

the electrical stimulation generator 1 for delivering the electric pulse

combination generated by the electrical stimulation generator 1 to the

individual, the structure of which is not limited in the present invention.

In detail, the electrode structures 2 have a contact surface, and the

contact surface contacts the skin of the user, and the contact position of

the user in the embodiment of the present invention is preferably the

abdominal skin.

Next, the frequency of the electric pulse combination will be

described. Please refer to FIG. 6, the electric pulse combination is

outputted sequentially from the first frequency group to the third

frequency group, the range of the first frequency group is preferably 10

to 20000 Hz, more preferably 13 to 18122 Hz, and the range of the

second frequency group is preferably 1 to 30 Hz, more preferably 1 to 28

Hz, and the range of the third frequency group is preferably 5 to 30 Hz,

more preferably 6 to 26 Hz. Wherein, the output time of the electric

pulse combination is preferably between 3520 to 3750 seconds, more

preferably 3633 seconds. The first frequency group has an output time

preferably between 2300 to 2350 seconds, more preferably 2312

seconds; the second frequency group has an output time preferably

between 900 to 1000 seconds, more preferably 949 seconds; and the

third frequency group has an output time preferably between 320 to 400

seconds, more preferably 372 seconds. The output frequency and output

time of the frequency range in the first frequency group, the second

frequency group, and the third frequency group can be adjusted according to actual needs without no limitation.

Particularly, in this embodiment, the first frequency group is

composed of 47 single-phase pulse groups, which sequentially includes

the first single-phase pulse group of 18122 Hz and output time of 7

seconds; the second single-phase pulse group of 10000 Hz and output

time of 15 seconds; the third single-phase pulse group of 7344 Hz and

output time of 19 seconds; the fourth single-phase pulse group of 5000

Hz and output time of 24 seconds; the fifth single-phase pulse group of

4200 Hz and output time of 26 seconds; sixth single-phase pulse group

of 3672 Hz and output time of 28 seconds; seventh single-phase pulse

group of 3175 Hz and output time of 30 seconds; eighth single-phase

pulse group of 3000 Hz and output time of 31 seconds; the ninth

single-phase pulse group of 2127 Hz and output time of 36 seconds; the

tenth single-phase pulse group of 2112 Hz and output time of 35

seconds; the eleventh single-phase pulse group of 2007 Hz and output

time of 30 seconds; the twelfth single-phase pulse group of 1865 Hz and

output time of 37 seconds; the thirteenth single-phase pulse group of

1850 Hz and output time of 37 seconds; the fourteenth single-phase

pulse group of 1550 Hz and output time of 39 seconds; the fifteenth

single-phase pulse group of 1234 Hz and output time of 42 seconds; the

sixteenth single-phase pulse group of 1043 Hz and output time of 44

seconds; the seventeenth single-phase pulse group of 1000 Hz and

output time of 45 seconds; the eighteenth single-phase pulse group of

921 Hz and output time of 45 seconds; the nineteenth single-phase pulse

group of 880 Hz and output time of 47 seconds; the twentieth

single-phase pulse group of 867 Hz and output time of 46 seconds; the

twenty-first single-phase pulse group of 807 Hz and output time of 45

seconds; the twenty-second single-phase pulse group of 778 Hz and

output time of 57 seconds; the twenty-third single-phase pulse group of

751 Hz and output time of 49 seconds; the twenty-fourth single-phase

pulse group of 730 Hz and output time of 45 seconds; the twenty-fifth

single-phase pulse group of 705 Hz and output time of 48 seconds; the

twenty-sixth single-phase pulse group of 668 Hz and output time of 54

seconds; the seventh single-phase pulse group of 652 Hz and output time of 55 seconds; the twenty-eighth single-phase pulse group of 625 Hz and output time of 54 seconds; the twenty-ninth single-phase pulse group of

612 Hz and output time of 51 seconds; the thirtieth single-phase pulse

group of 595 Hz and output time of 54 seconds; the thirty-first

single-phase pulse group of 542 Hz and output time of 57 seconds; the

thirty-second single-phase pulse group of 522 Hz and output time of 53

seconds; the thirty-third single-phase pulse group of 484 Hz and output

time of 55 seconds; the thirty-fourth single-phase pulse group of 462 Hz

and output time of 56 seconds; the thirty-fifth single-phase pulse group

of 435 Hz and output time of 60 seconds; the thirty-sixth single-phase

pulse group of 421 Hz and output time of 56 seconds; the thirty-seventh

single-phase pulse group of 380 Hz and output time of 60 seconds; the

thirty-eighth single-phase pulse group of 348 Hz and output time of 55

seconds; the thirty-ninth single-phase pulse group of 302 Hz and output

time of 60 seconds; the fortieth single-phase pulse group of 160 Hz and

output time of 69 seconds; the forty-first single-phase pulse group 141

Hz and output time of 65 seconds; the forty-second single-phase pulse group of 125 Hz and output time 72 of seconds; the forty-third single-phase pulse group of 95 Hz and output time 76 of seconds; the forty-fourth single-phase pulse group of 80 Hz and output time of 78 seconds; the forty-fifth single-phase pulse group of 66 Hz and output time of 75 seconds; the forty-sixth single-phase pulse group of 40 Hz and output time of 85 seconds; and the forty-seventh single-phase pulse group of 13 Hz and output time of 105 seconds. Furthermore, the second frequency group consists of 9 single-phase pulse groups, which sequentially includes the forty-eighth single-phase pulse group of 9 Hz and output time of 106 seconds; the forty-ninth single-phase pulse group of 6 Hz and output time of 110 seconds; the fiftieth single-phase pulse group of 1 Hz and output time of 133 seconds; the fifty-first single-phase pulse group of 28 Hz and output time of 72 seconds; the fifty-second single-phase pulse group of 19 Hz and output time of 72 seconds; the fifty-third single-phase pulse group of 10 Hz and output time of 24 seconds; the fifty-fourth single-phase pulse group of 8 Hz and output time of 144 seconds; the fifty-fifth single-phase pulse group of 6 Hz and output time of 144 seconds; and the fifty-sixth single-phase pulse group of 5 Hz and output time of 144 seconds. Finally, the third frequency group consists of 5 single-phase pulse groups, which sequentially includes the fifty-seventh single-phase pulse group of 6 Hz and output time of 144 seconds; the fifty-eighth single-phase pulse group of 7 Hz and output time of 144 seconds; the fifty-ninth single-phase pulse group of 8 Hz and output time of 36 seconds; the sixtieth single-phase pulse group of 17 Hz and output time of 36 seconds; and the sixty-first single-phase pulse group of 26 Hz and output time of 12 seconds.

In this embodiment, the single-phase pulse groups in the first

frequency group are outputted sequentially, and when the previous

frequency ends, the next frequency will be lower than the previous

frequency. However, the second frequency group may include a first

frequency variation group and a second frequency variation group,

wherein the number of the single-phase pulse groups in the first

frequency variation group is less than the number in the second

frequency variation group. Specifically, the range of the first frequency variation group is preferably 10 to 1 Hz, more preferably 9 to 1 Hz, and has an output time preferably between 300 to 360 seconds, more preferably 349 seconds. The range of the second frequency variation group is preferably 30 to 4 Hz, more preferably 28 to 5 Hz, and has an output time preferably between 550 to 650 seconds, more preferably 600 seconds.

Continuing from the above, the first frequency variation group

sequentially outputs the forty-eighth single-phase pulse group of 9 Hz,

the forty-ninth single-phase pulse group of 6 Hz and the fiftieth

single-phase pulse group of 1 Hz. Wherein when the previous frequency

ends, the next frequency will be lower than the previous frequency; the

second frequency variation group outputs sequentially the fifty-first

single-phase pulse group of 28 Hz, the fifty-second single-phase pulse

group of 19 Hz, The fifty-third single-phase pulse group of 10 Hz, the

fifty-fourth single-phase pulse group of 8 Hz, the fifty-fifth single-phase

pulse group of6 Hz, and the fifty-sixth single-phase pulse group of 5 Hz.

Wherein when the previous frequency ends, the next frequency will be lower than the previous frequency. Then, in this embodiment, the single-phase pulse groups in the third frequency group is outputted sequentially, and when the previous frequency ends, the next frequency will be higher than the previous frequency.

Specifically, the range of the potential difference generated by the

electric pulse combination is less than 1OVpp, wherein the potential

difference used in the present invention is a voltage potential difference,

and similarly, the potential difference used in the present invention can

be common in the technical field including peak-to-peak voltage (Vpp),

maximum voltage (Vmax) or root mean square voltage (Vrms). The

range of the potential difference is preferably less than or equal to

7.2Vpp. The electric stimulation system 1000 of the present invention

can stably output the voltage potential difference within the

aforementioned range and provide the user with a range of voltage

potential differences suitable for the human body.

In this embodiment, the electrical stimulation system 1000 can be

used to improve symptoms of diabetes, which include stabilizing blood glucose fluctuations or reducing inflammation.

In this embodiment, the electrical stimulation system 1000 can be

used for diabetic patients to stabilize blood glucose fluctuations, wherein

stabilizing blood glucose fluctuations is to reduce glycemic variability

(GV).

In this embodiment, the electrical stimulation system 1000 can be

used for diabetic patients to reduce inflammation, wherein reducing

inflammation is to reduce the protein expression of C-reactive protein

(CRP) and fibroblast growth factor 21 (FGF-21), which also has the

potential to reduce fibrosis.

In this embodiment, there is also a method using the

above-mentioned electrical stimulation system for diabetic patients, the

method includes generating an electric pulse combination that can

stabilize blood glucose fluctuations and reduce inflammation.

Embodiment 1

[Stabilizing blood glucose fluctuations]

To verify the feasibility of the present invention, the human experiment design of improving diabetes-related diseases was performed first. This experiment was a multi-center, prospective, double-blind, randomized, placebo-controlled trial (clinical trial number: NCT03102424), in which patients with type 2 diabetes were given the electrical stimulation system of the present invention (with electric pulse combination shown in FIG. 6) to improve blood glucose control of the patients. The type 2 diabetic patients who met all the inclusion criteria and did not meet the exclusion criteria were enrolled as subjects and randomly divided into a group using the electrical stimulation system of the present invention (hereinafter referred to as the

TENS group) and a placebo group in a ratio of 1:1, wherein the subjects

of the placebo group were given ineffective electrical stimulation. The

method was to attach the electrode structures of the electrical stimulation

system of the present invention to the left and right sides of the subject's

abdominal skin respectively one hour after dinner, one hour a day and at

least five-days a week for twenty weeks. The subjects checked their

blood glucose 7 times a day (before and 2 hours after each meal and at bedtime) on week 0, 4, 12, and 20 as self-monitoring of blood glucose

(SMBG).

The test results of the electrical stimulation system of this

embodiment are shown in Table 1.

Table 1

Baseline (Week 0) Week 20 TENS Placebo TENS Placebo

HbA lc, % 8.1 8.1 7.9 7.8

Mean 7-point SMBG 184 180 173 172

MAGE, mg/dL 85 88 66 79

CRP, mg/dL 0.22 0.24 0.16 0.38

FGF-21, mg/dL 0.29 0.35 0.24 0.32

In detail, in the embodiment of the present invention, the mean

amplitude of glycemic excursion (MAGE) was calculated using 7-point

SMBG data, which is an index representing glycemic variability (GV).

As shown in FIG. 2 and Table 1, the results showed that after 20 weeks

of electrical stimulation treatment, the 7-point SMBG of the TENS

group dropped from 184 at the baseline to 173, and that of the placebo

group dropped from 180 at the baseline to 172; and after calculation, the

MAGE of the TENS group decreased from 85 at the baseline to 66, while that of the placebo group decreased from 88 at the baseline to 79. It can be realized that in the TENS group, from week 0 to week 20, the changes of 7-point SMBG and MAGE showed a downward trend, and the change of MAGE was statistically significant (P=0.009). Compared with the placebo group, it could maintain a relatively more stable blood glucose variability.

Next, the efficacy of the electrical stimulation system of the

present invention in different subject groups was further studied. As

shown in FIG. 3, after the TENS group and the placebo group were

treated with the electrical stimulation system of the present invention,

the data of MAGE especially in the subjects of the women group

(P=0.042), HbAlc >8.0% group (P=0.002), and BMI<26.9 kg/m2 group

(P=0.047), the decline results of the data have statistically significant

differences. It can be seen that the electrical stimulation system of the

present invention can reduce the MAGE value of diabetic patients and

has a remarkable efficacy of stabilizing blood glucose fluctuations.

Embodiment 2

[Reducing inflammation]

Next, the experiment analyzes whether there were differences in

the inflammatory factors expressed in the blood samples after the

subjects received the electrical stimulation system of the present

invention for 20 weeks. Please refer to FIG. 4 to FIG. 5 and Table 1 for

the results.

It showed that after the electrical stimulation treatment, the

C-reactive protein (CRP) protein level measured from the TENS group

decreased from 0.22 at the baseline state to 0.16, the placebo group

increased from 0.24 at the baseline state to 0.38, and the fibroblast

growth factor 21 (FGF-21) protein decreased from 0.29 at the baseline to

0.24, and in the placebo group, the FGF-21 protein decreased from 0.35

at the baseline to 0.32. The CRP and FGF-21 levels from week 0 to

week 20 in the TENS group significantly decreased compared to the

placebo group. From the data of the reduction of CRP and FGF-21

protein expression, it was found that the electrical stimulation system of

the present invention can reduce the inflammation and potentially reduce fibrosis by reducing inflammatory cytokines in diabetic patients, thereby preventing the complications of diabetes.

In the embodiment of the present invention, as shown in Table 1,

the results showed that after 20 weeks of electrical stimulation treatment,

the glycosylated hemoglobin (HbAlc) of the TENS group decreased

from 8.1 at the baseline to 7.9, and the HbAlc of the placebo group

decreased from 8.1 at the baseline to 7.8, it can be realized that the

expression level of HbAlc has no significant change in the TENS group

and the placebo group. Thus the efficacy of stabilizing blood glucose

fluctuations or reducing inflammation after using the electrical

stimulation system was independent of HbAlc.

In summary, the electrical stimulation system and its application

method of the present invention can effectively achieve the effects of

stabilizing blood glucose fluctuations and reducing glycemic variability

(GV), as well as the special effect of reducing inflammation that has not

been found in the prior art.

Although the present invention has been described in considerable detail regarding certain embodiments thereof, other embodiments are possible. Therefore, the spirit and scope of the appended claims should not be limited to the description of the embodiments contained herein.

Claims (8)

What is claimed is:

1. An electrical stimulation system, comprising:

an electrical stimulation generator used to generate an electric pulse

combination, wherein a frequency of the electric pulse combination

ranging from 1 to 20,000 Hz, and comprises a first frequency group, a

second frequency group, and a third frequency group, wherein the first

frequency group, the second frequency group, and the third frequency

group are respectively composed of multiple single-phase pulse groups,

wherein each single-phase pulse group has a duty cycle greater than or

equal to 50% and a waveform that is a square wave;

at least one electrode structure electrically connected to the

electrical stimulation generator and having a contact surface applied to

the skin of an individual to deliver the electric pulse combination;

wherein the electric pulse combination is outputted in sequence

from the first frequency group to the third frequency group, wherein the

first frequency group ranges from 10 to 20,000 Hz, sequentially includes

the first single-phase pulse group of 18,122 Hz, the second single-phase pulse group of 10,000 Hz, the third single-phase pulse group of 7,344

Hz, the fourth single-phase pulse group of 5,000 Hz, the fifth

single-phase pulse group of 4,200 Hz, the sixth single-phase pulse group

of 3,672 Hz, the seventh single-phase pulse group of 3,175 Hz, the

eighth single-phase pulse group of 3,000 Hz, the ninth single-phase

pulse group of 2,127 Hz, the tenth single-phase pulse group of 2,112 Hz,

the eleventh single-phase pulse group of 2,007 Hz, the twelfth

single-phase pulse group of 1,865 Hz, the thirteenth single-phase pulse

group of 1,850 Hz, the fourteenth single-phase pulse group of 1,550 Hz,

the fifteenth single-phase pulse group of 1,234 Hz, the sixteenth

single-phase pulse group of 1,043 Hz, the seventeenth single-phase

pulse group of 1,000 Hz, the eighteenth single-phase pulse group of 921

Hz, the nineteenth single-phase pulse group of 880 Hz, the twentieth

single-phase pulse group of 867 Hz, the twenty-first single-phase pulse

group of 807 Hz, the twenty-second single-phase pulse group of 778 Hz,

the twenty-third single-phase pulse group of 751 Hz, the twenty-fourth

single-phase pulse group of 730 Hz, the twenty-fifth single-phase pulse group of 705 Hz, the twenty-sixth single-phase pulse group of 668 Hz, the twenty-seventh single-phase pulse group of 652 Hz, the twenty-eighth single-phase pulse group of 625 Hz, the twenty-ninth single-phase pulse group of 612 Hz, the thirtieth single-phase pulse group of 595 Hz, the thirty-first single-phase pulse group of 542 Hz, the thirty-second single-phase pulse group of 522 Hz, the thirty-third single-phase pulse group of 484 Hz, the thirty-fourth single-phase pulse group of 462 Hz, the thirty-fifth single-phase pulse group of 435 Hz, the thirty-sixth single-phase pulse group of 421 Hz, the thirty-seventh single-phase pulse group of 380 Hz, the thirty-eighth single-phase pulse group of 348 Hz, the thirty-ninth single-phase pulse group of 302 Hz, the fortieth single-phase pulse group of 160 Hz, the forty-first single-phase pulse group of 141 Hz, the forty-second single-phase pulse group of 125

Hz, the forty-third single-phase pulse group of 95 Hz, the forty-fourth

single-phase pulse group of 80 Hz, the forty-fifth single-phase pulse

group of 66 Hz, the forty-sixth single-phase pulse group of 40 Hz, and

the forty-seventh single-phase pulse group of 13 Hz, the output time of the first frequency group is between 2300 and 2350 seconds, the second frequency group ranges from 1 to 30 Hz, sequentially includes the forty-eighth single-phase pulse group of 9 Hz, the forty-ninth single-phase pulse group of 6 Hz, the fiftieth single-phase pulse group of

1 Hz, the fifty-first single-phase pulse group of 28 Hz, the fifty-second

single-phase pulse group of 19 Hz, the fifty-third single-phase pulse

group of 10 Hz, the fifty-fourth single-phase pulse group of 8 Hz, the

fifty-fifth single-phase pulse group of 6 Hz, and the fifty-sixth

single-phase pulse group of 5 Hz, the output time of the second

frequency group is between 900 and 1000 seconds, and the third

frequency group ranges from 5 to 30 Hz, sequentially includes the

fifty-seventh single-phase pulse group of 6 Hz, the fifty-eighth

single-phase pulse group of 7 Hz, the fifty-ninth single-phase pulse

group of 8 Hz, the sixtieth single-phase pulse group of 17 Hz, and the

sixty-first single-phase pulse group of 26 Hz, the output time of the third

frequency group is between 320 and 400 seconds.

2. The electrical stimulation system of Claim 1, wherein the output time of the electric pulse combination is between 3520 and 3750 seconds.

3. The electrical stimulation system of Claim 1, wherein the

electric pulse combination has a potential difference, which is less than

1OVpp.

4. The electrical stimulation system of Claim 1, wherein the

electrode structure contacts the abdominal skin of the individual.

5. The electrical stimulation system of Claim 1, wherein the

electrical stimulation system is capable of improving symptoms of

diabetes, which includes stabilizing blood glucose fluctuations or

reducing inflammation.

6. The electrical stimulation system of Claim 5, wherein

stabilizing blood glucose fluctuations refers to reducing glycemic

variability (GV).

7. The electrical stimulation system of Claim 5, wherein reducing

inflammation refers to decreasing the protein expression of C-reactive

protein (CRP) and fibroblast growth factor 21 (FGF-21).

8. A method using the electrical stimulation system of any claims

of Claim 1 to Claim 7.