Fang Xiu-juan (方秀娟),Zheng Guo-xin (鄭國新),Huangfu Ye-hui (皇甫燁輝), Yu Nian-tang (俞年塘)Tonglu Hospital of Traditional Chinese Medicine,Zhejiang Province,Hangzhou 311500,China

Abstract

Keywords: Moxibustion Therapy; Moxa Stick Moxibustion; Heat-sensitive Moxibustion;Sensory Thresholds; Diabetes Mellitus, Type 2;Diabetic Neuropathies

According to the statistics of the International Diabetes Federation(IDF),the number of newly diagnosed diabetes patients worldwide is increasing at a rate of 7 million every year,and there will be 1.01 million newly diagnosed diabetespatients every year in China.Diabetes has become a common threat to human life and survival.The latest diabetes epidemiologicalsurvey results show that the prevalence of diabetes in adults in China is as high as 12.8%,and even higher in the elderly.In the elderly over 60 years old,20.4%are diabetic patients and 24.5%are pre-diabetes. At present, China has replaced India as the world's largest country of diabetes[1].Diabetic peripheral neuropathy(DPN)is one of the most common chronic complications of diabetes,with an incidence rate ashigh as60% to 90%,and those with no obvious symptoms account for 30% to 40%[2].Main manifestations of DPNare limb pain,hypesthesia,numb,scorching hot and ice-cold sensations,or presenting with spontaneous pain,hyperalgesia and allodynia.In severe cases, amputation is required. Therefore, study on the effective treatment for DPN is quite meaningful.In this study,we observed the clinical efficacy of heatsensitive moxibustion plus Western medicine in treating DPN,and compared it with acontrolgroup.

1 Clinical Materials

1.1 Diagnostic criteria

1.1.1 Diagnosis of diabetes

This study referred the diagnostic criteria for type 2 diabetesin Brief Commentson Diabetes Guideline 2014 of American Diabetes Association[3]:diabetes symptoms plusplasma glucose levelwas≥11.1 mmol/L at any time,or fasting plasma glucose level was≥7.0 mmol/L with fasting defined as no calorie intake for at least 8 h;or,in the oral glucose tolerance test,the 2 h plasma glucose level was≥11.1 mmol/L.1.1.2 Diagnostic criteria for DPN

The diagnostic criteria for DPN in this study were established according to theInternal Medicine[4].Those who met the above diagnostic criteria of diabetes;the duration of disease was less than 5 years;who met the following DPN symptoms and signs:①limb numb,pain;② tendon reflex weakened or disappeared;③ paraesthesia or sensory disorder;④exclusion of neuropathies caused by other reasons;⑤ abnormal vibration threshold.

1.2 Inclusion criteria

Those who met the above diagnostic criteria for type 2 diabetes;aged 30 to 70 years old;met medical ethics requirements,agreed to participate in this clinical trial and signed informed consent;patients with DPN of both lower limbs.

1.3 Exclusion criteria

Women during pregnancy or lactation;who had acute complicationsof diabetic ketoacidosis,etc.;those with severe damage of liver or kidney,or diseases of cardiovascular system(such as angina pectoris,myocardial infarction,multiple cerebral infarction and cerebral hemorrhage);patients with peripheral neuropathies caused by neurotoxic drugs,alcohol addiction,vitamin B1deficiency,chronic nephropathy,hereditary neuropathy or hyperthyroid myopathy.

1.4 Elimination and dropout criteria

Those who were found to have any of the exclusion criteria after being included;who were not treated as required in the trial;those dropped out during treatment.

1.5 Suspension criteria

Those had severe adverse reactions during treatment;those presenting with severe complications,or rapid deterioration of the disease.

1.6 Statistical methods

All data were statistically analyzed by SPSS version 19.0 statistical software.Measurement data with normal distribution and homogeneous variance were expressed as mean± standard deviation(±s).Paired samplet-test was applied in intra-group comparisons,and independent samplet-test wasapplied in betweengroup comparisons.Wilcoxon rank-sum test was used for those data in non-normaldistribution.Counting data were expressed as rate,and processed by Chi-square test.Wilcoxon rank-sum test was applied to the comparison of ranked data.P＜0.05 was considered to indicate a statistically significant difference.

1.7 Generaldata

We planned to recruit 30 cases in each group,calculated at a dropout rate of 15%,and a total of 70 cases were required.All participants were DPN patients enrolled from Tonglu Hospital of Traditional Chinese Medicine, Zhejiang Province,between January 2018 and June 2019.The design of this study was reviewed and approved by the Ethics Committee of Tonglu Hospital of Traditional Chinese Medicine. All 70 patients were divided into an observation group and a control group by sealed envelope method combined with the random number table method, with 35 cases in each group.During treatment,3 cases in the control group dropped out(2 patients were unable to take the medicine in time and 1 quitted due to taking Chinese medicine),and 4 cases in the observation group dropped out(2 patients were unable to take the medicine in time and the other 2 quitted due to heat-sensitive moxibustion treatment interruption).Finally,a total of 63 patients finished the study.There were no statistically significant differences in gender,average age,average duration of disease and average duration of DPN between the two groups before treatment (allP＞0.05),indicating that the two groups were comparable (Table 1).

2 Treatment Methods

All cases were actively controlled and treated following clinical guidelines for diabetes,and patients with hypertension,coronary heart disease,and diabetic nephropathy were treated accordingly.

2.1 Control group

Patients in the control group were given oral vitamin B1,20 mg/time,3 times a day; mecobalamin tablets,0.5 mg/time,3 times a day.Fourteen days of continuous treatment was considered as a treatment course, with a 2-day interval between two courses.The efficacy wasassessed after 2 treatment courses.

2.2 Observation group

The observation group was treated with heat- sensitive moxibustion on the basis of the treatment in the controlgroup.

Acupoints:Zusanli(ST 36),Sanyinjiao(SP 6),Yinlingquan(SP 9),Yanglingquan(GB34),Xuehai(SP10),Fenglong (ST 40),Jiexi(ST 41), Taixi(KI3), Kunlun(BL 60)and Yongquan(KI1).

Table 1.Comparison of general data between thetwo groups

Methods:Heat-sensitive moxa sticks with a diameter of 40 mm were selected for moxibustion. The physician sought heat-sensitized points first. During moxibustion,when the patient felt no topical heat but distal heat away from the treated area [e.g. some DPN patients did not feel topical heat during moxibustion at Zusanli(ST 36), but gained heat sensation around eyes], or had topical feelings of soreness, distention or pain around the moxibustion area(that was,a moxibustion sensation of non-heat feeling), that point would be the heat-sensitized point.Then the physician performed mild moxibustion at the heat-sensitized points till the heat sensitization like heat penetration, heat expansion,soreness, distention and pain disappeared, which was considered as a dose of moxibustion.The time to complete a dose of moxibustion to the heat-sensitized point varied from person to person,in the range of 15-60 min, generally about 40 min. The moxibustion time was determined by the disappearance of the moxibustion response.

Some DPN patients had abnormal sensations about heat-sensitive moxibustion. Therefore, it was necessary to prevent burns due to hypoesthesia. The physician should promptly remove the moxa ash, and place the index finger and middle finger on the sides of the moxibustion area to sense the skin temperature of the patients, so as to adjust the moxibustion distance in time.

The treatment was performed for the observation group once a day, 14 d as a treatment course, with a 2-day interval between two courses, for 2 courses in total.

3 Observation of Curative Efficacy

3.1 Observation items

3.1.1 Clinical symptomsand signs

Toronto clinical scoring system(TCSS)was scored before treatment and after 2 treatment courses by one same physician for clinical symptoms and physical signs.TCSS was mainly composed of neurological discomfort symptoms,physiological nerve reflexes and sensory function scores.The highest score for neurological discomfort symptoms,physiological nerve reflex and sensory function was 6, 8 and 5 points,respectively,making a total score of 19 points. 6-8 points stood for mild peripheral neuropathy, 9-11 points for moderate and 12-19 points for severe.3.1.2 Vibration perception threshold(VPT)detection

Before treatment and after 2-course treatment, in a quiet environment,VPT was detected by one same tester using a VPT detector (Beijing Oerhuatai Technology Co., Ltd., China).

The patient took a supine position, with eyes closed and relaxed. The vibration frequency was 100 Hz. Firstly,the probe of VPT detector was placed at the plantar phalange of the great toe of patient's one foot, and the voltage was gradually increased from the initial low voltage of 5 V. The voltage value would be recorded when the patient could sense the vibration. Using the above detection methods, for one lower limb, the 1st,3rd and 5th metatarsophalangeal joints,the 3rd tarsometatarsal joint and the middle of the calcaneum bone at planta pedis were detected.Each point was detected once at an interval of 4 s, and the data were recorded. The average of the above 6 detection spots of this lower limb was calculated and regarded as its VPT value.According to the above detection method,6 identical points on the other lower limb were detected,and the average value was used as the VPT result of this lower limb.

Criteria of diagnosis:VPT lower than 15 V was considered as ‘no obvious DPN’; VPT between 15 V and 25 V was ‘mild DPN’; VPT higher than 25 V was ‘severe DPN’.

3.2 Criteria of curative efficacy

According to the criteria of curative efficacy for VPT in theGuiding Principles for Clinical Study of New Chinese Medicines[5],combined with clinical practice,the efficacy criteria of this study were established.

Cured: The pain, numbness and burning sensation of the limbs disappeared;the knee tendon reflex was normal, and there were no obvious clinical symptoms and signs. VPT was lower than 15 V.

Markedly effective:Clinical symptoms and signs significantly improved, and the knee tendon reflex was basically normal. VPT was between 15 V and 20 V.

Effective: The clinical symptoms and signs improved,while the knee tendon reflex was partially improved,and. VPT was between 20 V and 25 V.

通過多變量相關(guān)分析發(fā)現(xiàn)，3類生態(tài)系統(tǒng)中植物生物量與露石出露面積占比以及碎石含量之間相關(guān)關(guān)系不顯著(P>0.05)。物種組成與環(huán)境因子CCA分析得到4個排序軸，模型檢驗(yàn)顯著(F=2.3，P=0.002)。蒙特卡洛置換檢驗(yàn)表明前兩個軸物種與環(huán)境因子的相關(guān)系數(shù)分別為0.67和0.51，這說明環(huán)境變量能夠很好地解釋物種構(gòu)成。同時檢驗(yàn)發(fā)現(xiàn)0～20 cm土壤含水量環(huán)境因子不顯著(P>0.05)，固不納入模型分析。

Invalid:Clinical symptoms and signs had no improvement. VPT was higher than 25 V.

3.3 Results

3.3.1 Comparison of the clinical efficacy

The comparison result of the clinical efficacy between the two groups was presented asZ=3.837,P=0.000 by Wilcoxon rank-sum test,which suggested that the difference in clinical efficacy between the two groups was statistically significant,and the observation group was superior to the controlgroup(Table 2).

3.3.2 Comparison of the TCSS score

After treatment,the TCSS scores in both groups decreased compared with those before treatment, and the intra-group differences were statistically significant(bothP＜0.05),indicating that the patients’ symptoms in the two groups were significantly improved.Before treatment,there was no significant difference in the TCSS score between the two groups(P＞0.05).After treatment,the difference in the TCSS score between the two groups was statistically significant (P＜0.05),indicating that the improvements of patients’pain and numbness in the observation group were superior to those in the control group(Table 3).

3.3.3 Comparison of the VPT score

After treatment,the VPT scores in both groups decreased compared with those before treatment, and the intra-group differences were statistically significant(bothP＜0.05),indicating that patients’ sensations to the vibration in both groups were significantly improved.Before treatment, there was no significant difference in the VPT score between the two groups(P＞0.05).After treatment,the difference in the VPT score between the two groups was statistically significant (P＜0.05),indicating that the improvement of the vibration sensation in the observation group was superior to that in the controlgroup(Table 4).

Table 2.Comparison of the clinical efficacy between thetwo groups (case)

Table3.Comparison of the TCSSscore between the two groupsbefore and after treatment ( ±s, point)

Table3.Comparison of the TCSSscore between the two groupsbefore and after treatment ( ±s, point)

Group n Beforetreatment After treatment t-value P-value Observation 31 11.52±2.42 5.84±1.77 23.507 0.000 Control 32 11.56±2.44 8.19±2.12 12.930 0.000 t-value 0.000 3.590 P-value 1.000 0.001

Table4.Comparison of the VPT score between thetwo groups before and after treatment ( ±s, point)

Table4.Comparison of the VPT score between thetwo groups before and after treatment ( ±s, point)

Group n Beforetreatment After treatment t-value P-value Observation 31 20.48±3.27 12.87±2.27 22.602 0.000 Control 32 20.84±3.34 16.41±2.76 12.680 0.000 t-value 0.148 2.543 P-value 0.883 0.017

4 Discussion

According to the clinicalmanifestationsof DPN,it falls under the category of blood Bi-Impediment syndrome and vessel Bi-Impediment syndrome[6].Chinese medicine believes that DPN patients in early stage are mainly with qi(yang)deficiency and meridian blockage and blood stasis[7].The theories of blood stasis and collateral disease are the two major theories which guide the present treatment for DPN in Chinese medicine[8].

DPN is a complication with a high incidence in diabetes patients,and it is also an important factor causing the disability in diabetes.The present treatments of Western medicine for DPN are mainly drugs[13-15],and mostly are drug combination therapy[16-20].The treatment of DPN with integrated traditional Chinese and Western medicine can achieve the effect by various ways,such as nourishing nerves,anti-oxidative stress,improving microcirculation and correcting metabolic disorders[21-23].However,hospitalization and infusion will cause certain inconvenience and economic burden to patients.Heatsensitive moxibustion,also known as heat-sensitive suspended moxibustion,with‘new moxibustion therapy with acupoint heat-sensitization’as the full name,is a moxibustion therapy with simple operation and low cost.In this study,on the basis of oral Western medicine,the observation group was treated with heat-sensitive moxibustion at Zusanli(ST 36),Sanyinjiao(SP 6),Yinlingquan(SP9),Yanglingquan(GB34),Xuehai(SP 10),Fenglong (ST 40),Jiexi(ST 41),Taixi(KI 3),Kunlun(BL 60)and Yongquan(KI1) to warmly unblock the meridians and collaterals,activate blood and resolve stasis.

In this study,the curative efficacy was evaluated by quantitative scores of clinical symptoms and signs and VPT[24-28].The results suggested that heat-sensitive moxibustion plus Western medicine had a better curative efficacy than the Western medicine alone,with obvious advantages in improving the clinical symptoms and vibration sensitivity.It might be related to the improvement of local blood perfusion by heat-sensitive moxibustion,thereby reducing hypoxic-ischemic damage to the nerves[29].

In summary,heat-sensitive moxibustion plus Western medicine for DPN can improve the clinical symptoms,reduce limb numbness and sensation obstruction,with low cost and no pain for the patients,which is worth clinicalpromotion.

Conflict of Interest

There isno potential conflict of interest in thisarticle.

Acknowledgments

This work was supported by 2018 Science and Technology Planning Project of Traditional Chinese Medicine,Zhejiang Province (2018年浙江省中醫(yī)藥科技計劃項(xiàng)目, No.2018ZT004).

Statement of Informed Consent

Informed consent was obtained from all individual participants.

Received:23 February 2020/Accepted:26 March 2020