INTRODUCTION
According to the International Diabetes Federation (IDF), 537 million adults worldwide were already living with diabetes mellitus (DM) in 2021 and IDF estimates that there will be 783 million adults with diabetes by 2045. Diabetic distal sensorimotor polyneuropathy occurs in approximately 28% of hospitalized diabetic patients and in those in primary care, it is the most common neurological complication of DM. Moreover, diabetic peripheral neuropathy (DPN) can already occur in the presence of impaired glucose tolerance and thus before the manifestation of diabetes. DPN presents with stocking-like numbness, thermoanesthesia, hypesthesia, painful tingling, pricking, or burning sensations, and loss of proprioception. Especially hypesthesia and loss of proprioception may result in gait instability and falls; plantar injuries may go unnoticed and increase the risk for ulcerations or even amputation.
Pharmacological options to treat hypesthesia are missing. Symptomatic therapy addresses only plus-symptoms such as pain or tingling; here anticonvulsants and antidepressants are used. According to a Cochrane meta-analysis even strict glycemic control showed no recovery or prevention of neuronal demise[8] and the used anticonvulsants have common side effects like fatigue or interact with other medication. Previous studies have also shown that the adherence of patients with neuropathic pain to the standard dosage of the above-mentioned medications is poor; this has been explained by the fear of side effects or the inadequate control of pain. Non-pharmacological options for treatment are therefore of interest.
A meta-analysis in 2017 showed that acupuncture is an effective and safe treatment for chronic pain. Besides pain control, several trials suggest that acupuncture also has a positive influence on nerve function with an improvement of nerve conduction.
The acupuncture in DPN (ACUDPN) trial investigates the effectiveness of acupuncture in diabetic patients suffering from DPN with a follow up of the effects until week 24. The results of the primary subjective parameters were published elsewhere and showed that acupuncture may be beneficial with a significant and clinically relevant reduction of overall DPN-related complaints and pain and disease-specific quality of life. In this manuscript we focus on the effects of acupuncture on neurological examination scores and nerve conduction studies (NCS).
MATERIALS AND METHODS
This trial is a two-armed, randomized, controlled, parallel group, multicenter clinical trial. It was conducted between February 2019 and April 2021 at the German Charité Universitätsmedizin Berlin and at an outpatient clinic for TCM (HanseMerkur Center for TCM) at the University Medical Center Hamburg-Eppendorf in Hamburg, Germany. Details regarding study methodology have been published elsewhere.
Eligibility criteria
Participants had to meet the following criteria to be eligible for the study: Female or male aged 18-80 years; with a diagnosis of DPN with at least moderate symptoms and a minimum of at least 40 mm on a 0-100 mm visual analogue scale (VAS) for overall DPN-related complaints; pathological nerve conduction velocity (NCV) < 42 m/s and/or an amplitude of the sural nerve < 6 μV; absence of severe DPN with muscular weakness of the proximal leg muscles or neuropathy due to other reasons (such as borrelia infection, human immunodeficiency virus infection, hereditary factors, alcohol, or a history of neurotoxic drug use or traumatic lesions of the nerves or vessels in the lower extremities); body mass index < 35; absence of anticoagulation or bleeding disorders; absence of severe peripheral artery disease in Fontaine stage IV or ulcers or gangrenous lesions of the feet; severe fatigue syndrome; if needed then previously (since 4 wk) unchanged doses of pain medication against DPN; no opioid use before inclusion in the study or regular use of cannabis or cannabinoids or lipoic acid infusions planned during participation in the trial; no scheduled psychotherapy during study participation; no additional therapy with complementary medicine or physical therapy for symptoms of DPN during the 6 wk before inclusion in the study or planned during the study; no pregnancy or lactation. In addition, patients had to be able to complete a diary for the self-evaluation of symptoms, to record the use of symptomatic medication.
All patients were enrolled in the trial for 24 wk. The patients in the intervention group received a total of 12 acupuncture sessions over the first 8 wk, the control group was on a waiting list and received the same acupuncture treatment from week 16 onwards. All patients kept diaries for the first 8 wk, completed questionnaires, and attended follow ups. Both groups were allowed to continue their usual medication during the study. A detailed description of the methodology has been published elsewhere[19].
The main acupuncture points were inserted bilaterally . ST 40, LV3 and most of the EX-LE-10 “Bafeng” points are located in the innervation area of the peroneal nerve. SP 6 and KI 3 are located close to the tibial nerve.
Figure 1
Mandatory acupuncture points used in the acupuncture in diabetic peripheral neuropathy study. Anatomical presentation of acupuncture points in relation to major nerves of the lower extremity; A: Anterior aspect of leg with points on stomach-meridian 34 and 40; B: Medial aspect of ankle with point 6 on spleen-meridian and point 3 on kidney–meridian; C: Dorsal foot with point 3 on liver-merdian and extra-points lower-extremity. ST: Stomach-meridian; SP: Spleen-meridian; KI: Kidney–meridian; LV: Liver-merdian; EX-LE: Extra-points lower-extremity.
This research focuses on improvement of sensory loss assessed with patient reported outcomes, clinical and neurophysiological outcomes: Changes in the neuropathy symptom score (NSS), neuropathy deficit score (NDS), the clinical total neuropathy score (TNSc), and the patient questionnaire neuropathic pain symptom inventory (NPSI), which uses an 11-point scale to capture 5 different subdimensions of neuropathic pain which are sensitive to treatment. Since the NPSI does not assess hypesthesia, we added the 11-point numeric rating scale (NRS) for patients to rate the numbness sensation on the soles of the feet. All outcomes were assessed at 8, 16 and 24 wk.
The primary outcome of the ACUDPN trial was a VAS for overall DPN-related complaints including pain at week 8. The results of further secondary outcomes related to pain and quality of life were published elsewhere.
The evaluation yielded a difference of 2.3 (P < 0.001) in favor of the acupuncture group, an effect that persisted until week 16 with a difference of 2.2 (P < 0.001), which corresponds to 35.4% and 32.4% improvement for the intervention group compared to control at weeks 8 and 16 respectively (Figure 3). At week 24, in the acupuncture group the reduction of subjectively perceived hypesthesia was still 1.8 points lower than at baseline (Table (Table2).
Figure 3
11 point numeric ratings scale, neuropathic pain symptom inventory neuropathy deficit score, neuropathy symptom score, total neuropathy score clinical, week 8 and week 16. NRS-11: 11 point numeric ratings scale; NDS: Neuropathy deficit score; NSS: Neuropathy symptom score; TNSc: Total neuropathy score clinical.
Table 2
Overview of the outcome parameters
Outcome | Week | Acupuncture group adj. mean (95%CI) | Control group adj. mean(95%CI) | Difference adj. mean (95%CI) | P value |
NRS 11 numbness | 8 | 4.2 (3.1; 5.2) | 6.5 (5.4; 7.6) | 2.3 (1.3; 3.4) | < 0.001 |
16 | 4.6 (3.7; 5.6) | 6.8 (5.8; 7.9) | 2.2 (1.3; 3.1) | < 0.001 | |
NPSI | 8 | 17.4 (13.5; 21.4) | 30.0 (26.0; 34.0) | 12.6 (7.1; 18.0) | < 0.001 |
16 | 20.9 (16.2; 25.6) | 32.6 (27.8; 37.4) | 11.7 (5.0; 18.4) | < 0.001 | |
NDS | 8 | 7.0 (6.1; 8.0) | 8.1 (7.1; 9.1) | 1.0 (0.2; 1.9) | 0.021 |
16 | 7.3 (5.7; 9.0) | 8.2 (6.5; 9.9) | 0.9 (0.1; 1.7) | 0.035 | |
NSS | 8 | 6.3 (5.8; 6.8) | 7.6 (7.1; 8.1) | 1.3 (0.6; 2.0) | < 0.001 |
16 | 6.0 (4.1; 7.9) | 7.4 (5.4; 9.3) | 1.4 (0.4; 2.3) | 0.005 | |
TNSc | 8 | 7.8 (5.7; 9.8) | 9.8 (7.7; 11.9) | 2.0 (0.9; 3.1) | < 0.001 |
16 | 8.3 (6.8; 9.8) | 10.1 (8.5; 11.7) | 1.8 (0.5; 3.1) | 0.010 | |
N. suralis CV (m/s) | 8 | 38.2 (36.1; 40.4) | 38.6 (36.4; 40.7) | 0.4 (-2.7; 3.5) | 0.818 |
16 | 38.8 (33.5; 44.1) | 38.8 (33.6; 44.1) | 0.0 (-6.2; 6.3) | 0.988 | |
N. suralis ampl. (µV) | 8 | 3.8 (3.3; 4.4) | 4.4 (3.8; 4.9) | 0.6 (-0.2; 1.3) | 0.156 |
16 | 4.2 (3.5; 5.0) | 4.6 (4.0; 5.3) | 0.4 (-0.6; 1.4) | 0.428 |
NRS-11: 11 point numeric ratings scale; NPSI: Neuropathic pain symptom inventory; NDS: Neuropathy deficit score; NSS: Neuropathy symptom score; TNSc: Total clinical ceuropathy score; CV: Conduction velocity.
CONCLUSION
Study results suggest that acupuncture may be beneficial in type 2 diabetic DPN and seems to lead to a reduction in neurological deficits. No serious adverse events were recorded and the adherence to treatment was high. Confirmatory randomized sham-controlled clinical studies with adequate patient numbers are needed to confirm the results.
Reference:
Sebastian Hoerder, Isabel Valentina Habermann, Katrin Hahn, Gesa Meyer-Hamme, Miriam Ortiz, Weronika Grabowska, Stephanie Roll, Stefan N. Willich, Sven Schroeder, Benno Brinkhaus, and Joanna Dietzel. Acupuncture in diabetic peripheral neuropathy-neurological outcomes of the randomized acupuncture in diabetic peripheral neuropathy trial. World J Diabetes. 2023 Dec 15; 14(12): 1813–1823.
Published online 2023 Dec 15. doi: 10.4239/wjd.v14.i12.1813
PMCID: PMC10784801
PMID: 38222786
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