Manual Acupuncture or Combination with Vitamin B to Treat

Review ArticleManual Acupuncture or Combination with Vitamin B to TreatDiabetic Peripheral Neuropathy: A Systematic Review andMeta-Analysis of Randomized Controlled Trials

Hai lun Jiang ,1,2,3 Peng Jia,4 Yi hua Fan ,1,2,3 Meng dan Li,1,2,3 Can can Cao,1,2,3 Yuan Li,2

and Yu zheng Du 1,3

1First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China2Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China3National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300381, China4Tianjin Hospital, Tianjin 300221, China

Correspondence should be addressed to Yu zheng Du; [email protected]

Received 12 August 2020; Revised 14 October 2020; Accepted 2 November 2020; Published 21 November 2020

Academic Editor: Saber Khazaei

Copyright © 2020 Hai lun Jiang et al. This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background and Objective. The efficacy of mecobalamin (vitamin B12) alone in the treatment of diabetic peripheral neuropathy(DPN) is often unsatisfactory, while acupuncture treatment is also controversial. This study compares manual acupuncture tovitamin B in DPN treatment. Methods. Randomized controlled trials on manual acupuncture treatment of DPN were retrievedfrom the Medline, Web of Science, PubMed, Cochrane Library, EMBASE, CNKI, WanFang, and VIP databases. Extractedresearch data were summarized in the tables, and methodological assessment was performed using the risk-of-bias assessmenttool of Cochrane. Meta-analysis was performed by Revman 5.3, Stata 14.0, and TSA 0.9.5.10 Beta software. Results. A total of 18randomized clinical trials (RCTs) were recruited: (1) 11 RCTs were acupuncture alone compared with vitamin B; (2) 7 RCTswere acupuncture combined with vitamin B compared with vitamin B, involving 1200 participants. Acupuncture aloneimproved clinical efficacy (P < 0:05) and nerve conduction velocity of the four peripheral nerves: peroneal nerve, tibial nerve,median nerve, and ulnar nerve (P < 0:05), but there was no significant difference between the group of acupuncture alone andthe group of vitamin B (P = 0:36 > 0:05) in improving median nerve SCV (sensory nerve conduction velocity). Acupuncturecombined with vitamin B improved clinical efficacy and nerve conduction velocity of the three peripheral nerves, peronealnerve, tibial nerve, and median nerve (P < 0:05), and decreased the scores of the Toronto clinical scoring system (TCSS)(P < 0:05). Conclusion. Acupuncture alone and vitamin B combined with acupuncture are more effective in treating DPNcompared to vitamin B. However, more high-quality RCTs on vitamin B combined with acupuncture are required to confirmour results.

1. Introduction

Diabetic peripheral neuropathy (DPN) has been described as“signs and symptoms of peripheral nerve dysfunction inpatients with diabetes mellitus (DM) after the exclusion ofother causes” [1]. Physical pain, numbness, decreased sensa-tion, or other abnormal sensations are the main symptoms.Chronic distal symmetric polyneuropathy (DSPN) is themost common diabetic neuropathy [1]. An epidemiologicalstudy found that DPN prevalence is 7% for patients with type

1 diabetes and 22% for type 2 diabetes [2]. Most patients whowere diagnosed with DPN present with pain, but a consider-able number of patients without pain as a symptom weremisdiagnosed and therefore did not receive adequate andtimely treatment [3]. Mecobalamin is recommended for thetreatment of DPN in patients with type 2 DM according tothe China Food and Drug Administration guideline [4].Although duloxetine and pregabalin are still the drug ofchoice (DOC) for treating painful diabetic neuropathy(PDN), adverse drug reactions in the cardiovascular system

HindawiBioMed Research InternationalVolume 2020, Article ID 4809125, 15 pageshttps://doi.org/10.1155/2020/4809125

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https://doi.org/10.1155/2020/4809125

and digestive system have often been reported with signifi-cant safety concerns [5].

The prevention and management of DPN currently focusprimarily on glucose control [6], while the signs and symp-toms of DPN are always overlooked. In China, acupunctureis regarded as a “relatively safe” therapy, which is widelyaccepted with a long history, good reliability, feasibility, andease of operation [7]. It was frequently used for treating con-ditions in the nervous system to avoid the severe side effectsof chemical drugs.

Nerve conduction velocity is the gold standard to diag-nose DPN [8], and TCSS is an effective tool for screeningDPN with three domains including the neurological symp-tom score, neurological reflex score, and sensory functionscore to assess the DPN patient’s symptoms and/or signs.TCSS is highly consistent with the neuroelectrophysiologicalfunction where lower scores indicate greater relief [9, 10].

DPN is considered by traditional Chinese medicine asone of “Bi Zheng (arthralgia syndrome)” or “Wei zheng(flaccidity syndrome)” under a larger category of “Xiao Ke(consumptive disease).” DPN is caused by blockage of “Qiand Xue (Qi and blood)” from perfusing limbs and muscles;then, it impedes the nourishment of meridians [11]. At thispoint, acupuncture can be applied to adjust the “Qi andXue (Qi and blood)” of the human body and dredge themeridians [12]. So far, the RCTs on acupuncture treatmentof DPN are poorly designed, with a generally poor methodo-logical quality. What is more, no randomized controlled clin-ical trial from a multicenter has been published. Only twosystematic reviews have been published, one of which ana-lyzed articles until April 2013 while the other review analyzedarticles up to June 2017 [13, 14]. However, neither article hasfurther in-depth analysis of heterogeneous indicators. Somelimitations of these two studies include the following: (1)not all of the included articles were RCTs; (2) most of the par-ticipants had diabetic peripheral neuropathic pain (DPNP)and hence could not represent most DPN; and (3) Chinesedatabases were not searched [12]. In this review, we solelyused RCT data to evaluate the efficacy of acupuncture treat-ment on DPN. We compared the application of combiningacupuncture and vitamin B with vitamin B or compared acu-puncture alone with vitamin B in treating DPN, respectively.

2. Materials and Methods

2.1. Study Registration. This protocol of systematic reviewand meta-analysis has been drafted under the guidance ofthe Preferred Reporting Items for Systematic Reviews andMeta-Analyses protocols (PRISMA-P). Moreover, it has beenregistered on the open science framework (OSF) on May 14,2020 (registration number: DOI 10.17605/OSF.IO/PZ5GC).

2.2. Search Strategy. Keywords such as “acupuncture,” “dia-betic peripheral neuropathy,” and “DPN”were used to searchagainst databases including Medline, Web of Science,PubMed, Cochrane Library, EMBASE, CNKI, WanFang,and VIP, for RCTs, systematic reviews, or meta-analysespublished by April 5, 2020. There were no language restric-tions. The two investigators independently reviewed all liter-

ature to determine its inclusion (Hai lun Jiang and Peng Jia).Disagreements were adjudicated by a third investigator (Yihua Fan). The meta-analysis was conducted following theguidelines of Preferred Reporting Items for SystematicReviews and Meta-Analyses (PRISMA). The search strategyof EMBASE and CNKI is listed in Table S1, and PubMedsearch history is listed in Table S3

2.3. Inclusion Criteria

(1) Patients with diabetic peripheral neuropathy.

(2) RCT studies comparing manual acupuncture withvitamin B in the treatment of DPN; the manual acu-puncture study group includes both acupuncturealone and acupuncture coupled with vitamin B; thecontrol group was treated only with chemical drugs,and vitamin B must be included.

(3) Primary outcome: (1) clinical efficacy. Secondaryoutcomes: (1) motor nerve conduction velocity(MCV) of the peroneal nerve; (2) sensory nerve con-duction velocity (SCV) of the peroneal nerve; (3)motor nerve conduction velocity (MCV) of the tibialnerve; (4) sensory nerve conduction velocity (SCV) ofthe tibial nerve; (5) motor nerve conduction velocity(MCV) of the median nerve; (6) sensory nerve con-duction velocity (SCV) of the median nerve; (7)motor nerve conduction velocity (MCV) of the ulnarnerve; and (8) Toronto clinical scoring system(TCSS). Supplementary explanation: the definitionof clinical efficacy was not similar among trials. Theincluded trials’ clinical efficacy evaluation was basedon the following criteria [15]:

(1) Effectiveness. Symptoms and/or signs of peripheralnerve dysfunction improved, and MCV or SCVincreased.

(2) Ineffectiveness. Symptoms and/or signs of peripheralnerve dysfunction had not improved, or MCV orSCV did not obviously improve.

When the effect of symptoms and/or signs is inconsistentwith the effect of nerve conduction velocity, the lower effec-tive parameter is applied to show the comprehensive effect.

2.4. Exclusion Criteria

(1) Duplicated published articles

(2) Nonhuman limb acupoints

(3) Incomplete data from the articles

(4) The trials were rated as low quality by Zhao et al.’scriteria [16]

2.5. Data Extraction. Two independent investigators (Hai lunJiang and Peng Jia) separately extract data, involving thename of authors, year of publication, sample size, age of par-ticipants, duration of DPN, intervention measures, interven-tion time, outcome indicators, reinforcing and reducing,

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acupoints, and needle retaining time. When disagreementsoccurred, two independent investigators (Hai lun Jiangand Peng Jia) discussed to resolve the issues. If disagree-ments persisted, then the third investigator (Yi hua Fan)was consulted to make the final decision. Additional infor-mation was obtained by contacting authors directly via callor email.

2.6. Risk-of-Bias Assessments. Two independent reviewers(Hai lun Jiang and Peng Jia) evaluated the quality of theincluded RCTs separately, based on the Cochrane risk-of-bias criteria [17]. When disagreements occurred, two inde-pendent investigators (Hai lun Jiang and Peng Jia) discussedto resolve the issues. If disagreements persisted, then thethird investigator (Yi hua Fan) was consulted to make thefinal decision.

2.7. Data Synthesis and Statistical Analysis. In this meta-anal-ysis, the Revman 5.3 (developed by the UK’s InternationalCochrane Collaboration) and Stata 14.0 (developed by theUSA’s StataCorp LLC) software were used for analysis. Rela-tive risks (RR) were used to express dichotomous variables,whereas the mean difference (MD) and 95% confidenceinterval (CI) were used to denote continuous variables. Thechi-squared tests were used to assess statistical heterogeneity.When I2 < 50% or chi-squared test P ≥ 0:1, a fixed-effectmodel was applied. The source of heterogeneity was ana-lyzed, when I2 > 50% or chi-squared test P < 0:1. In theabsence of clinical heterogeneity or methodological heteroge-neity, the random-effect model was applied. Statistical signif-icance was set at P < 0:05. To test publication bias, Egger’stest was performed. Moreover, a sensitivity analysis was con-ducted to test the stability of the results.

Besides, trial sequence analysis using TSA 0.9.5.10 Beta(developed by the Copenhagen Trial Unit’s Centre forClinical Intervention Research) was used to calculate theappropriate sample size for the meta-analysis and to assessthe statistical boundaries for futility and efficacy. TheXaxisrepresents the sample size (participants),Yaxis representsthe statisticZvalues, two symmetrical red curves representthe boundary value of trial sequence analysis (TSA boundaryvalue), and symmetrical red horizontal dashed lines repre-sent the conventional boundary values (Z = 1:96,P = 0:05(two-sided)). If the cumulativeZvalue does not cross theTSA boundary value or RIS, it indicates that the sample sizeis insufficient, to recommend continuing the series of exper-iments. If the cumulative Z value exceeds both the TSAboundary value and the RIS, then the sample size is sufficient.If the cumulative Z value exceeds the TSA boundary valueand does not reach the RIS, it means that a reliable conclu-sion can be drawn in advance even if the sample size is insuf-ficient. According to the TSA method, when the cumulativeZ value has crossed the RIS, or the cumulative Z value inter-sects the TSA boundary value, the series of tests can be rec-ommended to stop (TSA parameter setting: type I errorprobability 5%, type II error probability of 20%, and the rel-ative risk reduction (RRR = −15%), to estimate the requiredinformation size (RIS)) [18].

3. Results

A total of 18 articles were selected, and the process is shownin Figure1 [19–36].

Only 7 of 18 randomized trials reported methods of ran-domization. No trial reported allocation concealment. Blind-ing does not affect the measure of nerve conduction velocity(NCV), and only one study reported blinding in this analysis.15 trials showed low risk in blinding participants or outcomeassessment. All studies were of low risk of incomplete out-come data, selective reporting, or other bias. Figure 2 outlinesthe quality and risk-of-bias evaluation of the included studies.Risk-of-bias assessments are shown in Figure 2.

3.1. The Basic Characteristics of the Inclusion Study. Name ofauthor, year of publication, sample size, age of participants,duration of DPN, intervention measures, intervention time,and outcome indicators are summarized in Table 1, and acu-points, reinforcing and reducing, and needle retaining timeare summarized in Table 2.

3.2. Meta-Analysis Result. In the experimental group, “acu-puncture alone” means “the intervention measure containsmanual acupuncture, but without neurotrophic drugs” and“acupuncture+vitamin B” means “the intervention measurecontains manual acupuncture and vitamin B, but no otherneurotrophic drugs.”

In the control group, “vitamin B” means “the interven-tion measure contains vitamin B as the only neurotrophicdrug.”

3.2.1. Description of Statistical Results. Out of the 18 trialsretrieved from searching published RCTs and systematicreviews, 11 trials were acupuncture alone vs. vitamin Binvolving 699 participants (there are 356 participants in theacupuncture alone group and 343 participants in the vitaminB group) and 7 trials were acupuncture combined with vita-min B vs. vitamin B involving 501 participants (there are 266participants in the acupuncture+vitamin B group and 235participants in the vitamin B group).

3.2.2. Acupuncture Alone vs. Vitamin B (Figure 3). Eight out-come indicators were used to compare acupuncture alone tovitamin B. The pooled results exhibited significant differ-ences in clinical efficacy, peroneal nerve MCV, peronealnerve SCV, tibial nerve MCV, tibial nerve SCV, median nerveMCV, and ulnar nerve MCV (P < 0:05), respectively. Asshown in Figure 3, our findings suggest that acupuncturealone is more effective than using vitamin B in DPN(P < 0:05) therapy. There was no significant differencebetween the SCV of the median nerve of the acupuncturealone group and that of the vitamin B group (MD= 3:07,95% CI: 1.92-4.21, P = 0:36 > 0:05; tag 7 in Figure 3). In thisRCT, the efficacy of vitamin B (lipoic acid) in the treatmentof DPN was compared with that of acupuncture alone. Giventhat only one study was included in this outcome indicator,sensitivity analysis could not be carried out for furtherverification.

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3.2.3. Acupuncture+Vitamin B vs. Vitamin B (Figures 4 and5). Eight outcome indicators were used to compare acupunc-ture+vitamin B with vitamin B. The pooled results displayedsignificant differences in clinical efficacy, peroneal nerveMCV, peroneal nerve SCV, tibial nerve MCV, tibial nerveSCV, median nerve MCV, median nerve SCV, and Torontoclinical scoring system (P < 0:05). As shown in Figure 4,

our findings suggest that acupuncture combined with vita-min B is better than using vitamin B alone, in the treatmentof DPN.

Peroneal nerve exposure’s heterogeneity in MCV andSCV was high (I2 = 59%, I2 = 58%; Figure 4, tags 2 and 3),but all indexes were on the right of the invalid line. TheMCV and SCV of the peroneal nerve had no significant

Records identified throughdatabase searching

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(n = 7)

Records a�er duplicates removed(n = 670)

Records screened(n = 670)

Records excluded basedon titles and abstracts

(n = 600)

Full-text articlesassessed for eligibility

(n = 70)Full-text articles excluded:

Non-RCT(n = 3)

�e experimentintervention did not meet

the inclusion criteria(n = 40)

Less detailed data(n = 8)

Duplicated publication(n = 1)

Studies included inqualitative synthesis

(n = 18)

Studies included inquantitative synthesis

(meta-analysis)(n = 18)

Figure 1: Flow chart of study identification and selection.

Random sequence generation (selection bias)

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Han2016

Ji2010

Ji1998

Li2005

Li2011

Lu2016

Pan2014

Ren2007

Song2005

Wang2007

Wang2010

Wu2017

Yan2007

Yao2012

Zhao2007

Zhao2016

Zuo2010Allocation concealment (selection bias)

Blinding of participants and personnel (performance bias)

Blinding of outcome assessment (detection bias)

Incomplete outcome data (attrition bias)

Selective reporting (reporting bias)

Other bias

Figure 2: Risk-of-bias summary.


clinical heterogeneity or methodological heterogeneity. Wefurther conducted sensitivity analyses on MCV and SCV ofthe peroneal nerve, and the outcome was stable. Subgroupanalysis was conducted based on intervention time (<3months, ≥3months), indicating that heterogeneity wasderived from intervention time (Figure 5, tags 1 and 2). Bothshort- and long-term acupuncture treatment therapyenhanced peroneal nerve MCV and peroneal nerve SCV(P < 0:05). While some heterogeneity was present (Figure 5,tag 1), it was still within acceptable limits. Given that treat-ment time is associated with restoration of nerve conductionvelocity, there is still a need to determine the long-term

effectiveness of acupuncture as DPN often recur after treat-ment [37, 38].

The heterogeneity in the MCV of the median nerve washigh (I2 = 69%; tag 6 in Figure 4). Subgroup analysis con-ducted based on disease duration (≤3 years, >3 years)revealed heterogeneity in disease duration (Figure 5, tag 3).Acupuncture intervention can improve the MCV of themedian nerve for both short-time and long-time diseaseduration (P < 0:05).

3.2.4. Subgroup Analysis (Figure 6). In the study of clinicalefficacy, subgroup analysis was conducted based on the

Table 1: The characteristics of the included trials.

ReferencesSample size

(T/C)Age (year)

Disease duration(year)

Intervention Interventiontime (days)

OutcomeTreatment Control

Fei 2011 30/30T: 54 ± 1C: 55 ± 1

T: 2:43 ± 2:23C: 2:53 ± 0:34 Ac Mec (p.o) 30 (4), (5)

Han 2016 42/42T: 56.3C: 56.2

/ AcMec (p.o)+nimodipine

(p.o)56 (1), (2), (3)

Ji 2010 40/40T: 60:7 ± 4:26C: 62:2 ± 4:13

T: 3:77 ± 1:16C: 3:44 ± 1:29 Ac Mec (i.m) 28 (1), (4), (5)

Li 1998 31/22 /T: 3 weeks–2 yearsC: 3 weeks–2 years

Ac VitB1, B12 (i.m) 30 (1)

Li 2005 30/30 All: 56:1 ± 3:2 / Ac Mec (i.v) 120 (1), (2), (6)

Li 2011 14/14 / /Ac+Mec(p.o)

Mec (p.o) 45 (9)

Lu 2016 31/29T: 66 ± 7C: 64 + 7

T: 3:6 ± 1:3C: 3:5 ± 1:1 Ac

Lipoic acid(i.v.drip)+alprostadil

(i.v.drip)30

(1), (2), (3), (6),(7)

Pan 2014 42/42 / /Ac+Mec(p.o)

Mec (p.o) 90 (1)

Ren 2007 30/30T: 63:±12:58C: 60:±11:47

T: 5:64 ± 4:77C: 5:81 ± 4:38 Ac VitB1, B12 (i.m) 30 (2), (6)

Song 2005 22/20T: 58:9 ± 5:24C: 58:9 ± 5:24

T: 6:91 ± 3:15C: 6:33 ± 3:56 Ac

VitB12 (i.m)+VitB1, B6(p.o)

30 (1), (2), (8)

Wang 2007 50/30T: 55.8C: 56.1

T: 6.5C: 7

Ac+VitB VitB 30 (4), (5), (6), (7)

Wang 2010 34/32T: 56:1 ± 5:33C: 58:4 ± 8:52

T: 2:91 ± 2:38C: 2:86 ± 2:59

Ac+Mec(i.v)

Mec (i.v) 28 (2), (3), (6), (7)

Wu 2017 40/40T: 53:4 ± 8:31C: 52:9 ± 8:45

T: 2:62 ± 0:56C: 2:52 ± 0:48

Ac+Mec(p.o)

Mec (p.o) 14(1), (2), (3), (6),

(7), (9)

Yan 2007 46/42T: 46.7-74.98C: 46.5-75.6

T: 0.8-12.4C: 0.7-11.8

Ac+Mec(p.o)

Mec (p.o) 90 (1), (2), (3)

Yao 2012 40/40T: 54.5C: 53.4

T: 0.67C: 0.58

AcMec (p.o)+nimodipine

(p.o)28-56 (1), (2), (3)

Zhao 2007 30/30T: 62:±7:33C: 62:1 ± 7:93

T: 2:71 ± 2:58C: 2:61 ± 2:22 Ac Mec (p.o) 60 (1), (5)

Zhao 2016 30/30 All: 53 ± 9:2 All: 0:58 ± 0:25 AcMec (p.o)+nimodipine

(p.o)56 (1), (2), (3)

Zuo 2010 40/35T: 57.6C: 57.1

T: 8.7C: 8.5

Ac+Mec(i.v)

Mec (i.v) 28 (2), (3), (6), (7)

Abbreviation: T: experimental group; C: control group; Ac: acupuncture; Mec: mecobalamin; p.o: per os; i.m: intramuscular vitamins; i.v: intravenous injection;i.v.drip: intravenous drip; Vit: vitamin. (1) Clinical efficacy; (2) the MCV of the peroneal nerve; (3) the SCV of the peroneal nerve; (4) the MCV of the tibialnerve; (5) the SCV of the tibial nerve; (6) the MCV of the median nerve; (7) the SCV of the median nerve; (8) the MCV of the ulnar nerve; (9) Torontoclinical scoring system (TCSS).


duration of the disease (≤3 years and >3 years) (Figure 6, tag 1).The result showed that acupuncture alone in the short- or long-term duration of the disease was better than using vitamin B(P < 0:05). We further conducted another subgroup analysisbased on drugs used in the control group (with microcircula-tion drugs and no microcirculation drugs) (Figure 6, tag 2).The result showed that acupuncture alone was better than

using vitamin B or vitamin B combined with microcirculationdrugs (P < 0:05).

3.3. Trial Sequence Analysis (Figures 7 and 8). The TSA ofacupuncture alone revealed that the cumulative Z-curvecrossed the conventional boundary value (Z = 1:96, P = 0:05(two-sided)) and TSA boundary value and met the RIS (554

Table 2: The characteristics of manual acupuncture.

References Acupoints Reinforcing and reducingNeedle retaining

time

Fei 2011Zusanli (ST36), Sanyinjiao (SP6), Pishu (BL20), Shenshu (BL23),

Weiwanxiashu (EX-CA)Mild supplementing and

reducing30min

Han 2016Houxi (SI13), Zhaohai (KI6), Zhaohai (KI6), Neiguan (PC6),Waiguan (TE5), Gongsun (SP4), Lieque (LU7), Lieque (LU7)

Mild supplementing andreducing

30min

Ji 2010Zusanli (ST36), Sanyinjiao (SP6), Quchi (LI11), Yanglingquan (GB34),

Hegu (LI4), Zhongwan (RN12), Xuehai (SP10), Diji (SP8),Yinlingquan (SP9), Fenglong (ST40), Taichong (LR3)


30min

Li 1998Zusanli (ST36), Sanyinjiao (SP6), Quchi (LI11), Yanglingquan (GB34),

Fenglong (ST40), Taibai (SP3)⟶Zutonggu (BL66)Mild supplementing and

reducing20min

Li 2005Zusanli (ST36), Sanyinjiao (SP6), Quchi (LI11), Yanglingquan (GB34),Pishu (BL20), Hegu (LI4), Dazhui (DU14), Weiwanxiashu (EX-CA),

Shenshu (BL23), Neiguan (PC6), Xuanzhong (GB39)


20-30min

Li 2011Quchi (LI11), Pishu (BL20), Hegu (LI4), Houxi (SI13), Shenshu (BL23),Xiawan (RN10), Zhongwan (RN12), Qihai (RN6), Guanyuan (RN4),

Ganshu (BL18)


15min

Lu 2016Zusanli (ST36), Pishu (BL20), Shenshu (BL23), Geshu (BL17),

Weiwanxiashu (EX-CA), Ganshu (BL18), Taixi (KI3), Ashi pointMild supplementing and

reducing30min

Pan 2014

Zusanli (ST36), Sanyinjiao (SP6), Quchi (LI11), Yanglingquan (GB34),Pishu (BL20), Hegu (LI4), Houxi (SI13), Shenshu (BL23), Ganshu (BL18),

Guanyuan (RN4), Qihai (RN6), Zhongwan (RN12), Xiawan (RN10),Yinlingquan (SP9), Diji (SP8), Jiexi (ST41), Yongquan (KI1)


20min

Ren 2007Zusanli (ST36), Sanyinjiao (SP6), Quchi (LI11), Yanglingquan (GB34),Fengchi (G20), Waiguan (TE5), Weizhong (BL40), Fenglong (ST40),

Taichong (LR3), Xuehai (SP10)


20min

Song 2005 Zusanli (ST36), Sanyinjiao (SP6), Pishu (BL20), Feishu (BL13)Mild supplementing and

reducing30min

Wang 2007Zusanli (ST36), Quchi (LI11), Yanglingquan (GB34), Hegu (LI4),Neiguan (PC6), Yangchi (TE4), Taichong (LR3), Jiexi (ST41)

/ 40min

Wang 2010Zusanli (ST36), Sanyinjiao (SP6), Quchi (LI11), Yanglingquan

(GB34), Jiexi (ST41), Neiting (ST44), Taixi (KI3), Guanyuan (RN4),Geshu (BL17), Ashi point


30min

Wu 2017Sanyinjiao (SP6), Taixi (KI3), Weiwanxiashu (EX-CA), Feishu (BL13),

Weishu (BL21), Shenshu (BL23)Mild supplementing and

reducing/

Yan 2007

Zusanli (ST36), Sanyinjiao (SP6), Quchi (LI11), Yanglingquan(GB34), Pishu (BL20), Taichong (LR3), Neiting (ST44), Jiexi (ST41),

Xingjian (LR2), Yinlingquan (SP9), Erjian (LI2), Sanjian (LI3),Yangxi (LI5), Yemen (TE2), Zhongzhu (TE3), Qiangu (SI2), Houxi (SI13),

Daling (PC7), Weiwanxiashu (EX-CA)


20min

Yao 2012Houxi (SI13), Neiguan (PC6), Gongsun (SP4), Waiguan (TE5),Lieque (LU7), Zhaohai (KI6), Lieque (LU7), Zhaohai (KI6)


30min

Zhao 2007Zusanli (ST36), Sanyinjiao (SP6), Quchi (LI11), Yanglingquan (GB34),Pishu (BL20), Hegu (LI4), Weiwanxiashu (EX-CA), Shenshu (BL23),

Feishu (BL13), Taixi (KI3), Ganshu (BL18)


30min

Zhao 2016Houxi (SI13), Zhaohai (KI6), Zhaohai (KI6), Waiguan (TE5),Neiguan (PC6), Lieque (LU7), Gongsun (SP4), Lieque (LU7)


30min

Zuo 2010Zusanli (ST36), Sanyinjiao (SP6), Quchi (LI11), Hegu (LI4),Taixi (KI3), Waiguan (TE5), Guanyuan (CV4), Qihai (CV6)


60min


cases) (Figure 7). This result means that the cumulative sam-ple size meets expectations; no more trials were needed.

The TSA of acupuncture combined with vitamin Brevealed that the cumulative Z-curve crossed the conven-

tional boundary value (Z = 1:96, P = 0:05 (two-sided)) butdid not reach the TSA monitoring boundary and RIS (2921cases) (Figure 8). This means that the cumulative sample sizedid not meet expectations; more trials were needed.

Han2016 403830252620382528

270296

196283

424031303122403030

273315181814331622

424022302920403030

0.5 0.7 1 1.5 2

Study or subgroup Acupuncture alone

1. Clinical efficacy

Acupuncture alone

Total (95% CI)Total eventsHeterogeneity: chi2 = 7.67, df = 8 (P = 0.47); I2 = 0%Test for overall effect: Z = 6.37 (P < 0.00001)

Ji2010Li1998Li2005Lu2016Song2005Yao2012Zhao2007Zhao2016

TotalEventsVitamin B

Vitamin B

WeightTotalEvents

Risk ratioM-H, fixed, 95% CI

13.5% 1.48 [1.17, 1.87]1.15 [0.98, 1.35]1.42 [1.06, 1.90]1.39 [1.00, 1.94]1.35 [0.98, 1.87]1.30 [0.95, 1.78]1.15 [0.98, 1.35]1.56 [1.08, 2.26]1.27 [1.01, 1.61]

1.32 [1.21, 1.43]

16.5%8.8%9.0%9.3%7.3%

16.5%8.0%

11.0%

100.0%

Risk ratioM-H, fixed, 95% CI

Han2016 47.8 5.2 42.3 4.1

225 221

42 42

–10 –5 0 5 10

Study or subgroup

Acupuncture alone

Total (95% CI)Heterogeneity: tau2 = 8.71, chi2 = 48.95, df = 6 (P < 0.00001); I2 = 88%Test for overall effect: Z = 4.02 (P < 0.00001)

Li2005Lu2016

Song2005Yao2012

Ren2007

Zhao2016

TotalAcupuncture alone

Mean SDVitamin B

Vitamin B

WeightTotalMean SDMean difference

IV, random, 95% CIMean difference

IV, random, 95% CI

14.6%

14.6%13.6%

13.6%14.6%14.7%

5.50 [3.50, 7.50]46.98

45.4548.21

49.54748

3.513.844.07

4.822.18

5 446

43.9644.9443.9138.55 3.98

4343

5.12

5.51

30

30 30

303040

3040

22

3130

20

29

40

14.3% 3.02 [0.80, 5.24]3.27 [1.27, 5.27]

1.54 [–1.08, 4.16]10.95 [8.98, 12.92]

4.00 [2.02, 5.98]5.00 [2.42, 7.58]

4.79 [2.46, 7.13]100.0%

Han2016 35.850.18

3536

6.33.25

67

31.53.67

52

45.895.1

143 141

42314030

3232

4229

–10 –5 0 5 10Acupuncture alone

Total (95% CI)Heterogeneity: chi2 = 0.81, df = 3 (P = 0.85); I2 = 0%Test for overall effect: Z = 6.99 (P < 0.00001)

Lu2016Yao2012Zhao2016

Vitamin B

20.6%40.0%21.1%18.2%

4.30 [1.85, 6.75]4.29 [2.53, 6.05]3.00 [0.58, 5.42]4.00 [1.39, 6.61]

3.97 [2.85, 5.08]100.0%

Ji2010Fei2011

Zhao2007

38.3539.9538.35

3.144.213.14

35.4938.7935.49

2.03

2.034.2

90 90

303030

303030


Total (95% CI)Heterogeneity: chi2 = 2.05, df = 2 (P = 0.36); I2 = 2%Test for overall effect: Z = 5.85 (P < 0.00001)

Vitamin B

41.7%16.5%41.7%

2.86 [1.52, 4.20]

2.86 [1.52, 4.20]1.16 [–0.97, 3.29]

2.58 [1.71, 3.44]100.0%

–10 –5 0 5 10Acupuncture aloneVitamin B

Ji2010Fei2011

Zhao2007

33.4338.08

45.36 42.9143.1543.15

46.385.38

46.87

37.83

1.833.974.12

31.6435.9836.98

1.75

1.673.375.24

3.974.28

100 100

30

30

3031

91

4030


Total (95% CI)Heterogeneity: chi2 = 0.85, df = 2 (P = 0.65); I2 = 0%Test for overall effect: Z = 4.51 (P < 0.00001) Vitamin B

68.8%18.7%12.5%

32.1%50.5%17.4%

1.79 [0.88, 2.70]2.10 [0.36, 3.84]

0.85 [–1.28, 2.98]

1.73 [0.98, 2.48]100.0%

100.0%


304030

30

3029

89

Li2005Lu2016Ren2007

2.955.57

2.45 [0.43, 4.47]3.23 [1.62, 4.84]3.72 [0.98, 6.46]

3.07 [1.92, 4.21]Total (95% CI)Heterogeneity: chi2 = 0.62, df = 2 (P = 0.73); I2 = 0%Test for overall effect: Z = 5.26 (P < 0.00001)

Total (95% CI)Heterogeneity: not applicableTest for overall effect: Z = 0.92 (P = 0.36)

46.3447.28 3.8231

31

100.0%29

29

Lu2016 4.06 0.94 [–1.05, 2.93]

100.0% 0.94 [–1.05, 2.93]

Song2005


Total (95% CI)Heterogeneity: not applicableTest for overall effect: Z = 11.77 (P < 0.00001)

39.4550.77 2.3322

22

100.0%20

20

3.79 11.32 [9.44, 13.20]

100.0% 11.32 [9.44, 13.20]

2. The MCV of peroneal nerve

Mean differenceIV, fixed, 95% CIStudy or subgroup Total

Acupuncture aloneMean SD

Vitamin B WeightTotalMean SDMean differenceIV, fixed, 95% CI

3. The SCV of peroneal nerve







4. The MCV of tibial nerve

5. The SCV of tibial nerve




6. The MCV of median nerve




7. The SCV of median nerve




8. The MCV of ulnar nerve

Figure 3: Forest plot of acupuncture alone.


Study or subgroup

Pan2014Wu2017 35Yan2007 42

Vitamin B1. Clinical efficacy

4040 27 4046 31 42

42 20 4234.2%37.6%

28.3%1.30 [1.01, 1.66]1.24 [1.01, 1.51]

2.00 [1.45, 2.77]

Acupuncture+vitamin BEvents Total Events Total Weight Risk ratio

M-H, random, 95% CIRisk ratio

M-H, random, 95% CI

Total (95% CI) 128 124 100.0% 1.44 [1.10, 1.89]

0.5 0.7 1 1.5 2

Total events 117 78Heterogeneity: tau2 = 0.04, chi2 = 6.97, df = 2 (P = 0.03); I2 = 71%Test for overall effect: Z = 2.62 (P = 0.009) Vitamin B Acupuncture+vitamin B

Study or subgroup

Wang2010Wu2017 44.65Yan2007 52.14

Vitamin B

43.54046

3420.0%22.9%

33.5%4.24 [1.65, 6.83]7.61 [5.34, 9.88]

4.70 [3.40, 6.00]

Acupuncture+vitamin B

5.675.15

2.9Mean SD Total

40.4144.53

38.84042

326.155.65

Zuo2010 46.7 40 23.5% 6.91 [4.71, 9.11]5.93 39.79 353.66

2.5Mean SD Total Weight Mean difference


IV, random, 95% CI

Total (95% CI) 160 149 100.0% 5.80 [4.22, 7.37]

−10 −5 0 5 10Heterogeneity: tau2 = 1.49, chi2 = 7.25, df = 3 (P = 0.06); I2 = 59%Test for overall effect: Z = 7.20 (P < 0.00001) Vitamin B Acupuncture+vitamin B

Study or subgroup

Wang2010Wu2017 36.58Yan2007 51.44

Vitamin B

36.24046

3419.8%25.5%

32.0%5.04 [2.32, 7.76]6.23 [4.13, 8.33]

2.90 [1.40, 4.40]


6.545.18

3.5Mean SD Total

31.5445.21

33.34042

325.874.64

Zuo2010 40.69 40 22.7% 3.41 [1.02, 5.80]6.42 37.28 354.01



IV, random, 95% CI

Total (95% CI) 160 149 100.0% 4.29 [2.65, 5.93]


Study or subgroup

Wang2007Wang2010 48.9Wu2017 49.46

Vitamin B

48.153440

5026.4%23.2%

25.3%3.20 [1.01, 5.39]3.97 [1.29, 6.65]

7.24 [4.88, 9.60]


5.25.68

5.5Mean SD Total

45.745.49

40.913240

303.8

6.53Zuo2010 47.65 40 25.2% 7.31 [4.94, 9.68]6.13 40.34 404.59



IV, random, 95% CI

Total (95% CI) 164 142 100.0% 5.43 [3.27, 7.60]


Study or subgroup

Wang2007Wang2010 38.9Wu2017 46.59

Vitamin B

40.633440

5041.2%17.2%

20.4%2.70 [1.01, 4.39]4.03 [1.41, 6.65]

4.39 [1.98, 6.80]


3.86.21

4.11Mean SD Total

36.242.56

36.243240

303.2

5.73Zuo2010 41.82 40 21.2% 3.39 [1.03, 5.75]6.51 38.43 403.94


IV, fixed, 95% CIMean difference

IV, fixed`, 95% CI

Total (95% CI) 164 142 100.0% 3.42 [2.33, 4.51]

−10 −5 0 5 10Heterogeneity: chi2 = 1.53, df = 3 (P = 0.68); I2 = 0%Test for overall effect: Z = 6.17 (P < 0.00001) Vitamin B Acupuncture+vitamin B

Study or subgroup

Li2011Wu2017 6.22

Vitamin B

3.44014

62.8%37.2%

−2.07 [−2.96, −1.18]−1.90 [−3.05, −0.75]


1.891.4

Mean SD Total

8.295.3

4014

2.151.7

Mean SD Total Weight Mean differenceIV, fixed, 95% CI

Mean differenceIV, fixed, 95% CI

Total (95% CI) 54 54 100.0% −2.01 [−2.71, −1.30]

−4 −2 0 2 4Heterogeneity: chi2 = 0.05, df = 1 (P = 0.82); I2 = 0%Test for overall effect: Z = 5.59 (P < 0.00001) Acupuncture+vitamin B Vitamin B

Study or subgroup

Wang2007

Vitamin B

46.92 50 100.0% 7.80 [5.40, 10.20]


2.92Mean SD Total

39.12 306.31Mean SD Total Weight Mean difference


IV, random, 95% CI

Total (95% CI) 50 30 100.0% 7.80 [5.40, 10.20]

−10 −5 0 5 10Heterogeneity: not applicableTest for overall effect: Z = 6.37 (P < 0.00001) Vitamin B Acupuncture+vitamin B

Study or subgroup

Wang2007

Vitamin B

40.31 50 100.0% 6.18 [3.15, 9.21]


3.92Mean SD Total

34.13 307.9Mean SD Total Weight Mean difference

IV, fixed, 95% CIMean differenceIV, fixed, 95% CI

Total (95% CI) 50 30 100.0% 6.18 [3.15, 9.21]

−10 −5 0 5 10Heterogeneity: not applicableTest for overall effect: Z = 4.00 (P < 0.0001) Vitamin B Acupuncture+vitamin B

2. The MCV of peroneal nerve

3. The SCV of peroneal nerve

4. The MCV of tibial nerve

5. The SCV of tibial nerve

6. The MCV of median nerve

7. The SCV of median nerve

8. Toronto clinical scoring system (TCSS)

Figure 4: Forest plot of acupuncture+vitamin B.


Study or subgroup

3.23.1 <3 months

3.23.2 ≥3 monthsYan2007 52.14 5.15 46 44.53 5.65 42 17.1% 7.61 [5.34, 9.88]

Vitamin BAcupuncture+vitaminBMean SD Total Mean SD Total Weight Mean difference


1. Intervention time (the MCV of peroneal nerve)

Wang2010 43.5Wu2017 44.65Zuo2010 46.7

2.95.675.93

344040

38.840.4139.79

2.56.153.66

324035

51.7%13.1%18.1%

4.70 [3.40, 6.00]4.24 [1.65, 6.83]6.91 [4.71, 9.11]

Subtotal (95% CI) 114 107 82.9% 5.11 [4.08, 6.14]

160 149 100.0% 5.54 [4.60, 6.48]

Heterogeneity: chi2 = 3.38, df = 2 (P = 0.18); I2 = 41%Test for overall effect: Z = 9.73 (P < 0.00001)

Total (95% CI)Heterogeneity: chi2 = 7.25, df = 3 (P = 0.06); I2 = 59%Test for overall effect: Z = 11.58 (P < 0.00001)Test for subgroup differences: chi2 = 3.87, df = 1 (P = 0.05); I2 = 74.2%

Subtotal (95% CI) 46 42 17.1% 7.61 [5.34, 9.88]Heterogeneity: not applicableTest for overall effect: Z = 6.58 (P < 0.00001)

−10 −5 0 5 10VitaminB Acupuncture+vitaminB

Study or subgroup

2.30.1 <3 months

2.30.2 ≥3 monthsYan2007 51.44 5.18 46 45.21 4.86 42 23.2% 6.23 [4.13, 8.33]



2. Intervention time (the SCV of peroneal nerve)

Wang2010 36.2Wu2017 36.58Zuo2010 40.69

3.56.546.42

344040

33.331.5437.28

2.75.874.01

324035

45.2%13.8%17.8%

2.90 [1.40, 4.40]5.04 [2.32, 7.76]3.41 [1.02, 5.80]

Subtotal (95% CI) 114 107 76.8% 3.40 [2.25, 4.56]

160 149 100.0% 4.06 [3.05, 5.07]



Subtotal (95% CI) 46 42 23.2% 6.23 [4.13, 8.33]Heterogeneity: not applicableTest for overall effect: Z = 5.82 (P < 0.00001)


Study or subgroup

3.21.1 ≤3 years



3. Disease duration (the MCV of median nerve)

Wang2010 48.9Wu2017 49.46

5.25.68

3440

45.745.49

3.86.53

3240

29.6%19.7%

3.20 [1.01, 5.39]3.97 [1.29, 6.65]

Subtotal (95% CI) 74 72 49.3% 3.51 [1.81, 5.20]

160 142 100.0% 5.42 [4.23, 6.61]


3.21.1 >3 yearsWang2007 48.15Zuo2010 47.65

5.56.13

5040

40.9140.34

5.034.59

3040

25.5%25.2%

7.24 [4.88, 9.60]7.31 [4.94, 9.68]

Subtotal (95% CI) 90 70 50.7% 7.27 [5.60, 8.95]Heterogeneity: chi2 = 0.00, df = 1 (P = 0.97); I2 = 0%Test for overall effect: Z = 8.52 (P < 0.00001)



Figure 5: Acupuncture+vitamin B’s subgroup analysis forest plot.


3.4. Safety Analysis. Two RCTs [27, 36] reported no adverseevent, and no mention was made of the others.

3.5. Publication Bias. Egger’s test was performed to evaluatethe publication bias of the primary outcome. Nine studieswere evaluated for the clinical efficacy of acupuncture alone(Egger’s test: P = 0:005), and the results showed a statisticallysignificant difference. Besides, the statistical significance of

Egger’s test indicates publication bias. Three studies wereevaluated for the clinical efficacy of acupuncture combinedwith vitamin B (Egger’s test: P = 0:207), and the resultsrevealed no publication bias.

3.6. Sensitivity Analysis. Sensitivity analysis was performed totest the stability of the results, and the results showed that allindicators were stable.

Study or subgroup Acupuncture alone

Acupuncture alone

TotalEventsVitamin B

Vitamin B

WeightTotalEventsRisk ratio

M-H, fixed, 95% CIRisk ratio

M-H, fixed, 95% CI

Experimental groupControl group

1.5.1 ≤3years

Subtotal (95% CI)

Subtotal (95% CI)

Total eventsHeterogeneity: chi2 = 4.14, df = 4 (P = 0.39); I2 = 3%Test for overall effect: Z = 4.50 (P < 0.00001)

Li1998Yao2012Zhao2007Zhao2016

3038

382620

84 65

2528

121

31

31

40

40

3030

131

15

1818

33

33

1622

2293

224205 151

211

0.5 0.7 1 1.5 2

0.5 0.7 1 1.5 2

86122

2240

40292089

3030

11.3%21.3%

21.3%

42.8%

100.0%

12.0%9.5%

10.3%14.2%57.2%

1.42 [1.06, 1.90]1.15 [0.98, 1.35]

1.15 [0.98, 1.35]1.35 [0.98, 1.87]1.30 [0.95, 1.78]

1.15 [0.98, 1.35]1.42 [1.06, 1.90]1.39 [1.00, 1.94]1.30 [0.95, 1.78]1.56 [1.08, 2.26]1.33 [1.17, 1.51]

1.24 [1.08, 1.43]

1.28 [1.17, 1.40]

1.56 [1.08, 2.26]1.27 [1.01, 1.61]1.31 [1.16, 1.48]

Ji2010Lu2016Song2005

1.5.2 >3years

Total eventsHeterogeneity: chi2 = 1.18, df = 2 (P = 0.55); I2 = 0%Test for overall effect: Z = 2.99 (P = 0.003)

Total (95% CI)Total eventsHeterogeneity: chi2 = 5.07, df = 6 (P = 0.53); I2 = 0%Test for overall effect: Z = 5.17 (P < 0.00001) Test for subgroup differences: chi2 = 0.32, df = 1 (P = 0.57); I2 = 0%

1.10.1Acupuncture alone vs. vitamin B aloneJi2010Li1998Li2005Song2005Zhao2007

Subtotal (95% CI)

3830252025

4031302230

153138 96

3315181416

4022302030

142

16.5%8.8%9.0%7.3%8.0%

49.7%



1.48 [1.17, 1.87]1.35 [0.98, 1.87]1.15 [0.98, 1.35]1.27 [1.01, 1.61]1.30 [1.16, 1.46]

1.32 [1.21, 1.43]

1.10.2 Acupuncture alone vs. vitamin B+ microcirculation drugsHan2016Lu2016Yao2012Zhao2016

Subtotal (95% CI)

40263828

132

296270 196

283

42314030

143

27183322

42294030

141100

13.5%9.3%

16.5%11.0%50.3%

100.0%Total (95% CI)Total eventsHeterogeneity: chi2 = 7.67, df = 8 (P = 0.47); I2 = 0%Test for overall effect: Z = 6.37 (P < 0.00001) Test for subgroup differences: chi2 = 0.05, df = 1 (P = 0.82); I2 = 0%

1.Disease duration (the clinical efficacy)

Study or subgroup Experimental groupTotalEvents

Control group WeightTotalEventsRisk ratio

M-H, fixed, 95% CIRisk ratio

M-H, fixed, 95% CI

2.The using of microcirculation drugs (the clinical efficacy)

Figure 6: The clinical efficacy’s subgroup analysis forest plot.


4. Discussion

DPN pathogenesis involves interactions of multiple factors;hence, it is not yet clear. Since hyperglycemia is a well-known factor affecting many internal metabolic pathways,the key approach to DPN treatment is therefore strict control

of hyperglycemia. Additionally, abnormal lipid metabolism,insulin resistance, and neurotrophasthenia may also partici-pate in the metabolic pathway [39, 40]. Peripheral nerveedema, demyelination, and axonal degeneration are associ-ated with the deposition of catabolic blood glucose productson peripheral nerves [41, 42].

CumulativeZ-score

Favo

urs

vita

min

BFa

vour

sac

upun

ctur

e alo

ne

−8

RIS is a two-sided graph

RIS = 554

Z-curve−7

−6

−5

−4

−3

−2

−1

1

519 Number ofpatients

(linear scaled)

2

3

4

5

6

7

8

Figure 7: Trial sequence analysis of acupuncture alone (the clinical efficacy).

CumulativeZ-score

Favo

urs

vita

min

BFa

vour

sac

upun

ctur

e+vi

tam

in B

−8

RIS is a two-sided graph

RIS = 2921

−7

−6

−5

−4

−3

−2

−1

1

252 Number ofpatients

(linear scaled)

2

3

4

5

6

7

8

Z-curve

Figure 8: Trial sequence analysis of acupuncture+vitamin B (the clinical efficacy).


Vitamin B restores neurotrophic factors and repairsnerves, which is used as supplementary treatment of axonalcell damage and nerve demyelination changes. Mecobalamin,a form of vitamin B12 with a high neuronal affinity, wasshown to be able to repair the damaged myelin sheath andpromote axon regeneration [43]. However, the efficacy ofmecobalamin alone is often unsatisfactory in the treatmentof DPN [44]. Combination of multiple vitamin B [27, 28]has a protective effect on micrangium of diabetic patients[45] and alleviates the symptoms. The animal experimentdemonstrated that vitamin B1 can prevent abnormal lipidmetabolism [46]. Lipoic acid, a form of vitamin B-like com-pound, was a natural antioxidant and could improve nerveconduction velocity [47]. Compared with mecobalamin,lipoic acid was more effective in treating DPN [48]. In addi-tion, the combined use of neurotrophy medicine and drugsthat improve microcirculation, such as alprostadil, has dem-onstrated synergistic action (Figure 6, tag 3) in the treatmentof type 2 DM [49] and thus is recommended by the Chineseguideline [4]. Dilation of the vessels to enhance microcircula-tion is an important treatment mechanism [50].

Acupuncture exhibits a good therapeutic effect on DPNdue to its direct local effect on microcirculation and its rolein electrophysiological activity [51]. What is more, acupunc-ture can effectively reduce plasma neuropeptide Y (NPY)[52], which is one of the main risk factors for the develop-ment of type 2 diabetes via constriction of blood vesselsand changes in the metabolic environment of the body[53], especially on lipid metabolism [54]. Reducing plasmaneuropeptide Y (NPY) effectively delays the occurrence ofdiabetes and its complications [55]. Furthermore, acupunc-ture protects islet cells, increases insulin sensitivity, and pro-motes the secretion of insulin in diabetic patients to regulatethe patient’s blood glucose and lipid [56].

Our subgroup analysis indicates that acupuncture canachieve clinical efficacy in a short course of treatment whichshows a good curative effect on patients with duration ofDPN over 3 years. Of all included studies, Zusanli (ST36),Sanyinjiao (SP6), Quchi (LI11), and Yanglingquan (GB34),which are mainly distributed in the forearm and foreleg, arefrequently selected for stimulation. In 18 RCTs, their acu-point frequencies were 13, 12, 11, and 9, respectively. Anexamination found that the distal part of extremities is themost common lesion site [57]. It is consistent with thehypothesis that an “acupoint can be used to treat unusualsymptoms around this acupoint” [58].

It is related to their local anatomy structure, as these acu-points are close to the dorsal cutaneous nerve of the forearm,lateral sural cutaneous nerve, radial nerve, peroneal nerve,deep peroneal nerve, tibial nerve, etc. directly. Furthermore,an animal experiment showed that stimulating Zusanli(ST36) improves blood glucose regulation [59].

The onset and development of DPN can be explained asdeficiency in the root and excess in the branch, accordingto the basic theory of traditional Chinese medicine (TCM),deficiency of “Qi” and “Xue” is the root, and blood stasisand phlegm are the branches [60, 61]. Sanyinjiao (SP6) isthe location where the liver meridian, spleen meridian, andkidney meridian meet and can therefore nourish these three

zang-fu organs (kidney, liver, and spleen). Needling Sanyin-jiao (SP6) also harmonize “Qi” and “Xue” and balance Yin-Yang. Simply put, needling these acupoints can dredge themeridian and promote Qi and blood circulation. Ultimately,it relieves pain, numbness, and other symptoms, to achieve agood effect of DPN therapy. The results suggested that DPNshould be treated using acupuncture. And the result of trialsequence analysis shows that the sample size of RCTs on acu-puncture alone to treat DPN was enough but acupuncturecombined with vitamin B to treat DPN was not.

5. Limitations

(1) Only one of the 18 included trials was blind research,which might affect the evaluation of clinical efficacyaccording to the Cochrane Handbook. But it has noeffect on the measurement of nerve conduction velocity

(2) The number of the 18 included studies was small (atotal of 1200 participants were involved), and 17 trialswere in the Chinese language that may lead to publica-tion bias. Based on the result of trial sequence analysis,the sample size of RCTs on acupuncture combinedwith vitamin B to treat DPN was not enough

(3) Although the 18 RCTs showed that acupuncturealone and acupuncture combined with vitamin Bare more effective than vitamin B in the treatmentof DPN, there are some variations in acupuncturethat may cause different curative effects

(4) None of the studies reported long-term effects andsafety following acupuncture treatments

(5) There is no uniform international standard for thedefinition of clinical efficacy; the clinical efficacy eval-uation was based on guiding principles for clinicalresearch of new Chinese medicine [15]

6. Conclusions

The main role of acupuncture compared with vitamin B is toimprove clinical efficacy. Besides, acupuncture significantlyincreases nerve conduction velocity and decreases the scoresof the Toronto clinical scoring system (TCSS). However, fur-ther multicenter studies with large samples and high-qualityRCTs on acupuncture combined with vitamin B are required,to more reliably assess the effect of acupuncture on DPN.Meanwhile, it is necessary to set standard criteria for evaluat-ing clinical effectiveness.

Data Availability

We searched against databases and reviewed all literature andthen extracted data; additional information was obtained bycontacting authors directly via call or email.

Conflicts of Interest

All authors declare that there is no conflict of interest regard-ing the publication of this paper.


Authors’ Contributions

Hai lun Jiang and Peng Jia contributed equally to this work,and it is necessary to consider them as co-first authors.

Acknowledgments

The authors would like to thank freescience (http://www.home-for-researchers.com) for their help in improving theEnglish language. This research was supported by the Apo-plexy Acupuncture Inheritance Innovation Platform.

Supplementary Materials

Table S1: search strategy. Table S2: PRISMA checklist. TableS3: PubMed search history. Figure S1: the sensitivity analysisof clinical efficacy of acupuncture alone. Figure S2: the sensi-tivity analysis of the MCV of the peroneal nerve of acupunc-ture alone. Figure S3: the sensitivity analysis of the SCV of theperoneal nerve of acupuncture alone. Figure S4: the sensitiv-ity analysis of the MCV of the tibial nerve of acupuncturealone. Figure S5: the sensitivity analysis of the SCV of the tib-ial nerve of acupuncture alone. Figure S6: the sensitivity anal-ysis of the MCV of the median nerve of acupuncture alone.Figure S7: the sensitivity analysis of clinical efficacy of acu-puncture combined with vitamin B. Figure S8: the sensitivityanalysis of the MCV of the peroneal nerve of acupuncturecombined with vitamin B. Figure S9: the sensitivity analysisof the SCV of the peroneal nerve of acupuncture combinedwith vitamin B. Figure S10: the sensitivity analysis of theMCV of the median nerve of acupuncture combined withvitamin B. Figure S11: the sensitivity analysis of the SCV ofthe median nerve of acupuncture combined with vitamin B.(Supplementary Materials)

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