Sarcopenia and Diabetes: A Detrimental Liaison of Advancing Age

Round 1

Reviewer 1 Report

This paper reviews the relationship between sarcopenia and diabetes, which is an important topic. However, the paper is long and unfocussed. Please remember that the review is not meant to rehash T2DM treatment or sarcopenia diagnosis, but to focus specifically on the relationship between the two. The paper needs to be revamped completely with this in mind. Many paragraphs are very long, and are just one-line summaries of various papers without much synthesis, which is crucial in a narrative review. 

Overall comments

Many of the paragraphs are too long, and simply rehashes papers. More synthesis is required, and please make the paper more concise.

Introduction

The first paragraph is very long. Sections such as the Asian working group is redundant. Please shorten. There are also sentences/phrases that do not read well – ‘poor health’ is non specific. ‘sarcopenia MAY occur with one or more three specific criteria’ – this is not quite correct, and is contradicted by the following 2 sentences

The first line needs references.

Line 87-92 is too long. Please shorten. The paper is really about the bidirectional relationship between T2DM and sarcopenia and should be specified as such.

Line 92-101 needs to be in methods. Was this a systematic review? The search strategy needs to be included in appendix.

Section 2 – please be very clear that this section is to explore how the pathophysiology of T2DM may contribute to sarcopenia. Confounders and pathophysiology of sarcopenia not related to T2DM souold be in another section/excluded. So each section should have the following structure: XYZ is affected in T2DM. Through whatever mechanism, XYZ also causes sarcopenia. Please rewrite with this in mind. 

How is gut dysbiosis related to T2DM? Please describe. 

Line 138 – suboptimal protein intake is not actually a T2DM process – this is a confounder (like physical activity, socioeconomic status. Please put in another section.

Whilst figure 1 is helpful, the point of this review is to focus on mechanisms where hyperglycemia/T2DM results in sarcopenia. Please revamp.

Table 2 – how does vit D affect T2DM?

Section 3 – as above

Another section regarding confounders is needed. The relationship between sarcopenia and T2DM is significantly affected by confounding. The most important of these is physical activity, which is the strongest modifiable determinant of sarcopenia (after age which is not modifiable) & also significantly impacts glycemic control/obesity. Please see Foong et al, Accelerometer‐determined physical activity, muscle mass, and leg strength in community‐dwelling older adults, Journal Cachexia sarcopenia muscle 2016. 

Other confounders that require mentioning include socioeconomic status, obesity and diet amongst others. (see Foong et al, The association between physical activity and reduced body fat lessens with age—results from a cross-sectional study in community-dwelling older adults Experimental gerontology 2014).

Section 4 is too long and unfocussed. Focus on the interventions that target both T2DM and sarcopenia. Section 4.1 is irrelevant. Please rewrite and shorten significantly. 

4.2 is not proven yet, and probably more suited to a ‘future directions section’

4.4 where is the evidence for metformin/sulfonylureas in sarcopenia? The point of this paper is not to rehash the evidence for these drugs in T2DM which has been done numerous times. Focus on interventions that treat both.

Section 5 – is this meant to be a future directions section? If so please revise

Section 6 conclusion is way too long. What are the key take home messages?

as above

Author Response

Dear Reviewer,

Thanks for your comments and suggestions, allowing us to improve the organization and readability of the text. Please consider that the manuscript has been extensively revised and shortened, and some parts have been reorganized to better cope with your suggestions. Changes are in red. Here, you can find a point-to-point reply.

___________________________

1.  "The first paragraph is very long. Sections such as the Asian working group is redundant. Please shorten. There are also sentences/phrases that do not read well – ‘poor health’ is non specific. ‘sarcopenia MAY occur with one or more three specific criteria’ – this is not quite correct, and is contradicted by the following 2 sentences"

Less specific terms were removed, criteria revised, and redundant concepts deleted.

2. "The first line needs references."

The first line has now a specific reference.

3. "Line 87-92 is too long. Please shorten. The paper is really about the bidirectional relationship between T2DM and sarcopenia and should be specified as such."

The period was shortened and reorganized according to your suggestion.

4. "Line 92-101 needs to be in methods. Was this a systematic review? The search strategy needs to be included in appendix."

The paper is a comprehensive (narrative) review. Database searching strategy is now in the section "2. Methods".

5. "Section 2 – please be very clear that this section is to explore how the pathophysiology of T2DM may contribute to sarcopenia. Confounders and pathophysiology of sarcopenia not related to T2DM souold be in another section/excluded. So each section should have the following structure: XYZ is affected in T2DM. Through whatever mechanism, XYZ also causes sarcopenia. Please rewrite with this in mind."

Section 2 is now Section 3. The section was reorganized and shortened to be more concise and clear. Please check for details.

6. "How is gut dysbiosis related to T2DM? Please describe."

The relation between gut dysbiosis and T2D is summarized in section 3. Please check the text for details (changes are in red).

7. "Whilst figure 1 is helpful, the point of this review is to focus on mechanisms where hyperglycemia/T2DM results in sarcopenia. Please revamp."

Figure 1 has been adjusted to be clearer. Please consider that Figure 1 must be red as follows: risk factors predisposing to sarcopenia in T2D (red color above the horizontal red arrow); mechanism involved in diabetes-related sarcopenia (red color below the horizontal red arrow). The same applies to protecting/reverting factors and mechanisms (green).

8. "Table 2 – how does vit D affect T2DM?"

Vit-D deficiency is thought to impair insulin sensitivity. Vit-D supplementation is thought to improve insulin sensitivity rather than enhance insulin secretion (Xu, Z., Gong, R., Luo, G. et al. Association between vitamin D3 levels and insulin resistance: a large sample cross-sectional study. Sci Rep 12, 119 (2022).

9. "Section 3 – as above"

Section 3 is now Section 4. Please check the text for adjustments (changes are in red). 

10. "Another section regarding confounders is needed. The relationship between sarcopenia and T2DM is significantly affected by confounding. The most important of these is physical activity, which is the strongest modifiable determinant of sarcopenia (after age which is not modifiable) & also significantly impacts glycemic control/obesity. Please see Foong et al, Accelerometer‐determined physical activity, muscle mass, and leg strength in community‐dwelling older adults, Journal Cachexia sarcopenia muscle 2016. Other confounders that require mentioning include socioeconomic status, obesity and diet amongst others. (see Foong et al, The association between physical activity and reduced body fat lessens with age—results from a cross-sectional study in community-dwelling older adults Experimental gerontology 2014)."

Thanks for your suggestions. I agree with you about the critical role of physical inactivity as a modifiable risk factor for sarcopenia as well as T2D. You can find adjustments in the section 6 (Modifiable risk factors).

11. "Section 4 is too long and unfocussed. Focus on the interventions that target both T2DM and sarcopenia. Section 4.1 is irrelevant. Please rewrite and shorten significantly. 4.2 is not proven yet, and probably more suited to a ‘future directions section"

Section 4 has been reorganized. Section 5 discusses the assessment of skeletal muscle mass and strength with a concise presentation and one summarizing table. The assessment of skeletal muscle health is relevant when discussing sarcopenia in a field of medicine (Diabetology) in which there are no specific tools or codified procedures for assessing skeletal muscle health. The section 4.2 is now the section 7.1. It is more concise and explicative. Sections 7.2 and 7.3 of the current version are dedicated to non-pharmacological and pharmacological interventions. Both have been revised and shortened.

12. "4.4 where is the evidence for metformin/sulfonylureas in sarcopenia? The point of this paper is not to rehash the evidence for these drugs in T2DM which has been done numerous times. Focus on interventions that treat both."

Evidence for metformin and secretagogues are detailed and presented in section 6.3 Pharmacological intervention.

13. "Section 5 – is this meant to be a future directions section? If so please revise."

The section 5 is now section 8. It is titled "Future directions".

14. "Section 6 conclusion is way too long. What are the key take home messages?"

The section 6 is now section 9. Conclusion was rewritten to be more concise and indicate precise key messages.

Reviewer 2 Report

Dear Authors,

The review is very comprehensive, well written and has merit. I only have some suggestions:

Please, consider and assess the following comments and suggestions:

1. The references are too numerous of manuscript too general and not specific to the main question addressed.

2. In the current form of the manuscript there are no specific conclusions.

3. I suggest, change VD to Vit-D.

4. Table 3 is not visible.

Author Response

Dear reviewer,

Thanks for your comments and suggestions. 
The manuscript has been extensively revised. The overall length of the text and the number of references have been reduced. I replaced the abbreviation VD with Vit-D. Table 3 is now visible.

Round 2

Reviewer 1 Report

Thank you to the authors for the comprehensive point-by-point comments. Whilst many of my concerns have been addressed, I would strongly recommend making the review more concise. This would also improve readability. Entire sections and paragraphs can be removed, such as section 5. Section 5 whilst very interesting from a sarcopenia perspective, has little to do with the intersection between T2D and sarcopenia, which is what the paper is about. Another example that can be shortened is section 7.3. Please work closely with the editorial staff to make the article more succinct.

see above

Author Response

Dear Reviewer,
Thank you for the suggestions. We deleted section 5. Section 7.3 (now 6.3) was revised, shortened, and reorganized with subheadings to improve the readability of the text.