Exercise and Manual Therapy for Diabetic Peripheral Neuropathy: A Systematic Review
, Concepción Vidal-Peracho 1,3, Sergio Márquez-Gonzalvo 1,2, Jaime Corral-de-Toro 1,2, Julián Müller-Thyssen-Uriarte 1,2, Jacobo Rodríguez-Sanz 4,5, María Orosia Lucha-López 1,2,*, José Miguel Tricás-Moreno 1,2 and César Hidalgo-García 1,2Round 1
Reviewer 1 Report
This is a systematic review regarding efficacy of exercise and manual therapy for diabetic peripheral neuropathy (DPN). RCTs comparing manual therapy and/or exercise in patients on pain, function and/or balance were selected. PRISMA statement was followed. 656 articles registered and 29 were selected. There was little consensus on DPN criteria selection. Aerobic, strength and balance exercise are beneficial for DPN. Sessions of 30-60 min, 3 times per week for 8 weeks seems to be the most used dose. Manual therapy was effective at short-term. Combination of both modalities is more beneficial than alone.
This time-consuming study was conducted properly according to the PRISMA statement. The information is useful.
- However, the outcomes of trials were too various and it was difficult to interpret. It would be interesting to see the sub-analysis stratified according to the types of outcomes, e.g., pain, function or balance.
- In conclusion, the authors stated that “Regarding the combination of both therapies, no conclusion on this hypothesis can be drawn due to the lack of evidence available”. The statement “Combination of both modalities is more beneficial than alone” in the abstract should be corrected.
Author Response
We are grateful for the corrections suggested by the reviewer. You will find the responses to their comments in the attached pdf and with track changes in the new manuscript.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
Review: Exercise and Manual Therapy for Diabetic Neuropathy: A Systematic Review
COMMENTS
The systematic review is a good and informative try in a very difficult research field about exercise and diabetic neuropathy.
A major criticism is that authors did not report anything about the presence or absence of cardiovascular autonomic neuropathy, a major risk factor for the development of cardiovascular events. Only two reported studies (ref 38,40) mentioned that patients with autonomic neuropathy excluded. But, it is unreachable from a clinical perspective patients with peripheral neuropathy would not present in any degree and autonomic neuropathy. Furthermore, examination for cardiovascular autonomic neuropathy is essential before prescribing exercise, because patients could have reduced heart rate variability and in more severe cases a fixed, ‘’locked’’ heart rate. Moreover, if cardiovascular autonomic neuropathy had been diagnosed, ischemic heart disease should had been excluded, as suggested from many studies in the literature. So, the title from the review is wrong. It should be changed and it should referred to peripheral neuropathy only. Otherwise the review cannot be published. Moreover, cardiovascular autonomic neuropathy could lead to altered balance of the patients. Authors should add a paragraph with all the above mentioned comments as limitations of their review.
The definition of peripheral neuropathy is also missing in the manuscript.
I think that, the methodology is appropriate. The manuscript is generally clearly written and the discussion / conclusions are acceptable.
Overall, the data could be of interest, if authors add the above mentioned data.
Author Response
We are grateful for the corrections suggested by the reviewer. You will find the responses to their comments bellow and with track changes in the new manuscript.
Comments from the reviewers:
Reviewer 2:
The systematic review is a good and informative try in a very difficult research field about exercise and diabetic neuropathy.
A major criticism is that authors did not report anything about the presence or absence of cardiovascular autonomic neuropathy, a major risk factor for the development of cardiovascular events. Only two reported studies (ref 38,40) mentioned that patients with autonomic neuropathy excluded. But, it is unreachable from a clinical perspective patients with peripheral neuropathy would not present in any degree and autonomic neuropathy. Furthermore, examination for cardiovascular autonomic neuropathy is essential before prescribing exercise, because patients could have reduced heart rate variability and in more severe cases a fixed, ‘’locked’’ heart rate. Moreover, if cardiovascular autonomic neuropathy had been diagnosed, ischemic heart disease should had been excluded, as suggested from many studies in the literature. So, the title from the review is wrong. It should be changed and it should referred to peripheral neuropathy only. Otherwise the review cannot be published. Moreover, cardiovascular autonomic neuropathy could lead to altered balance of the patients. Authors should add a paragraph with all the above mentioned comments as limitations of their review.
Answer: The authors of this paper thank for the comments of the reviewer. In accordance with the reviewer's recommendations, the title of the review has been specified as diabetic peripheral neuropathy. In addition, a comment about the absence of selection criteria specifying diabetic neuropathy has been included in the Results (line 185-186) and Discussion section (line 798-802). And finally, a limitation of the study has been included in the lines 905-922.
The definition of peripheral neuropathy is also missing in the manuscript.
Answer: Definition was included on line 38 to 41.
I think that, the methodology is appropriate. The manuscript is generally clearly written and the discussion / conclusions are acceptable.
Overall, the data could be of interest, if authors add the above mentioned data.
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
The authors have responded to the comments appropriately.
