【原】【晨读】糖尿病周围神经病变的非药物治疗：综述（八）

 英语晨读 ·

山东省立医院疼痛科英语晨读已经坚持10余年的时间了，每天交班前15分钟都会精选一篇英文文献进行阅读和翻译。一是可以保持工作后的英语阅读习惯，二是可以学习前沿的疼痛相关知识。我们会将晨读内容与大家分享，助力疼痛学习。

本次文献选自Suzanne, Amato, Nesbit, et al. Non-pharmacologic treatments for symptoms of diabetic peripheral neuropathy: a systematic review.[J]. Current Medical Research & Opinion, 2018.35(1)：15-25. 本次学习由李芸主治医师主讲。

We identified no studies that compared or combined pharmacologic and non-pharmacologic approaches; combi-nations of therapies would be critical to study further, as these approaches are often used together in clinical practice. Better assessment of adverse effects would also allow better evaluation of the benefit-risk balance, rather than just evalu-ation of effectiveness. Studies should also follow guidelines for pain intervention studies and evaluation of outcomes.

我们没有发现可以比较或组合药理学和非药理学方法的研究。治疗的组合对于进一步研究至关重要，因为这些方法在临床实践中经常一起使用。不仅仅是评估有效性，还可更好地评估不利影响和利益风险平衡。研究还应遵循疼痛干预研究和结果评估的指南。

The last comprehensive review including non-pharmaco-logic treatments for diabetic peripheral neuropathy addressed literature through August 2008 and concluded that there were no effective treatments. Specifically, the review concluded that evidence was insufficient for alpha-lipoic acid or other supplements, that percutaneous electrical nerve stimulation should be considered, and that other methods should not be considered or had insufficient evi-dence. Although our review found a number of new studies for non-pharmacologic approaches for the treatments addressed in this review, as well as studies of new treat-ments, few approaches had evidence for effectiveness (Table 2). A recent position statement from the American Diabetes Association on diabetic neuropathy did not address non-pharmacologic treatments.

上一次综述包括非药物治疗糖尿病周围神经病变涉及的文献，截止至2008年8月，并得出结论，没有有效的治疗方法。特别是该综述得出结论，认为对于硫辛酸或其他补品而言证据不 足，应考虑经皮电神经刺激，不应考虑其他方法或证据不足的方法。尽管我们的综述发现了许多针对本综述所述治疗方法的非药物学方法的新研究，以及针对新疗法的研究，但很少有方法能证明其有效性（表2）。美国糖尿病协会关于糖尿病性神经病的最新立场声明未涉及非药物治疗。

We also identified several other systematic reviews for specific interventions for DPN, and these were generally con-sistent with our findings. Prior meta-analyses of RCTs of alpha-lipoic acid, including one addressing a larger literature from China, have also concluded that it is effective, although studies generally have limitations. A larger systematic review of manual acupuncture through March 2013 did not require a sham arm for inclusion and included 25 RCTs, but was unable to draw conclusions due to high risk of bias. A systematic review of surgical decompression through August 2006 identified no RCTs with appropriate controls. Although a meta-analysis of electrical stimulation and elec-tromagnetic stimulation concluded that TENS (but not electromagnetic fields) was effective, this review included a TENS study that we excluded since it was not focused only on diabetic neuropathy. Other systematic reviews of exercise including DPN also did not find RCTs addressing pain, pares-thesia, or numbness.

我们还针对DPN的特定干预措施确定了其他几项系统评价，这些评价与我们的发现基本一致。先前对α-硫辛酸的RCT进行的荟萃分析（包括一项针对中国较大文献的文献）也得出结论，尽管研究普遍存在局限性，但它是有效的。到2013年3月，对手动针灸进行了较大规模的系统评价，不需要假肢纳入，并且包括25个RCT，但由于偏倚风险较高，因此无法得出结论。到2006年8月，对手术减压的系统评价未发现有适当控制的RCTs。尽管对电刺激和电磁刺激的荟萃分析得出结论：认为TENS（而不是电磁场）是有效的，但该综述包括一项TENS研究，我们将其排除在外，是因为它不仅仅针对糖尿病性神经病。其他对运动的系统评价，包括DPN，也未发现针对疼痛、感觉异常或麻木的RCT。

Our review has several limitations. We focused only on studies in diabetic neuropathy, and evidence from treat-ments that are effective for other types of peripheral neur-opathy or other chronic pain conditions (e.g. exercise, physical therapy) could also be relevant. Some studies had unusually high calculated effect sizes, potentially based on limitations of the reported data; we included these studies in our review, but also evaluated results without them as a sen-sitivity analysis. We limited the review to studies with at least 3 weeks of follow-up, and to studies with sham or placebo arms, wherever appropriate. This excluded very short-term studies and studies where sham was possible but not used (especially for acupuncture). We also excluded non-English language publications, and this limited our scope for acu-puncture. Since we addressed the effectiveness of these interventions for diabetic peripheral neuropathy specifically, this review does not address the broader literature describ-ing harms of these interventions in different conditions. This broader safety data, such as overall mortality from spinal cord stimulation, is, therefore, not included in this report.

我们的综述也有几个局限性。我们只关注糖尿病神经病变的研究，对其他类型的周围神经病变或其他慢性疼痛疾病有效的治疗方案(如锻炼、物理治疗)也可能是相关的。某些研究具有异常好的治疗效果，可能基于报告数据的局限性；我们将这些研究也纳入在我们的综述中，没有敏感性分析的情况下也参考这些研究。我们将审查限制在至少有3周随访的研究，而不管其是否有对照组。这就将一些虽然有对照但随访时间非常短的研究排除在外了。我们还排除了非英语语言的出版物，这大大缩小了我们关于针灸的研究数据。由于我们专门讨论了这些治疗措施对糖尿病周围神经病变的有效性，而没有关注这些治疗措施在不同条件下的不良反应。因此本综述缺乏更全面的安全性数据，如脊髓电刺激的问题死亡率。

Conclusions

We concluded that spinal cord stimulation (although this has a risk of serious complications) and alpha-lipoic acid were effective for the outcome of pain (low strength of evidence), and transcutaneous electrical nerve stimulation and fre-quency-modulated electromagnetic stimulation were not effective (low strength of evidence); other treatments had insufficient evidence and require more research. Magnitudes of effect were generally moderate and all studies had deficits in quality. There were no studies evaluating exercise or phys-ical therapy, and only one evaluating cognitive behavioral therapy for pain. Additional studies evaluating longer-term outcomes, and those combining pharmacologic and non-pharmacologic approaches to maximize function are needed to better inform clinical decision-making, patient choice, and clinical practice guidelines.

结论

我们得出结论，脊髓电刺激(尽管有严重并发症的风险)和α-硫辛酸对缓解疼痛有效(证据强度低)，经皮神经电刺激和调频电磁刺激无效(证据强度低)；其他治疗方法证据不足，需要进一步研究。治疗效果大部分是中等的，而且研究都有质量缺陷。目前没有关于锻炼或物理疗法的研究，关于疼痛的认知行为疗法的研究只有一项。以后的研究应侧重于延长随访时间，以及药物学和非药物学方法的联合应用，以更好地为临床决策、患者选择和临床实践指南提供依据。