PONE-D-20-38516

Body Composition Trajectory and Association with Cardiometabolic Risk Factors: a Population-Based Cohort Study

PLOS ONE

Dear Dr. Liu,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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We look forward to receiving your revised manuscript.

Kind regards,

Yiqiang Zhan

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: No

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: I Don't Know

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: No

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Many thanks for the opportunity to review this manuscript. The comments below are intended as a constructive direction on improving the manuscript.

The manuscript will benefit from editing to tidy up grammar/spelling.

Reviewer #2: Overview

The authors present an interesting analysis which considers different patterns of change in fat to fat-free mass ratio (trajectories) across 16 years in a population-based cohort in China. They relate the different trajectories to cardiometabolic outcomes. I think the concept and the results are interesting however I have some major concerns about the discussion and some of the conclusions which have been drawn from the results.

Furthermore, it is sometimes difficult to follow the points being made (particularly in the introduction & discussion). It is essential that the whole manuscript undergoes a thorough proof reading to ensure that all statements are written correctly in English and make sense as they are written.

Introduction

Where the authors refer to ‘cardiovascular risk factors’, this includes dyslipidemia, diabetes, cholesterol and triglyceride measures; I would consider these as ‘cardiometabolic’ outcomes and suggest changing the general terminology throughout the manuscript.

It would be good to define the ‘trajectory effect’ more clearly and mention potential biological underpinning for the trajectory effect itself, not just the negative consequences of obesity.

F2MR, consider changing this to F2FFMR

Methods

The first paragraph states that the first wave was 1989, then the ‘study population’ paragraph says baseline was 1993- this is a bit confusing, when was baseline?

3013 were included- how many were originally seen? Or, put another way, how many were excluded? In the flow chart it looks like 2792 participants were seen in 1993, I’m not sure I understand how 3013 participants can be included in this analysis?

Please insert the reference for ‘guidelines for the prevention and treatment of dyslipidemia in Chinese adults’.

Was there any distinction between type-2 and type-1 diabetes?

Note to editor: The group‐based trajectory modelling method was applied to the longitudinal body fat data using maximum likelihood method for model fitting and parameter estimation. I believe these are sound methods, however, I am not familiar with using them in my own work and therefore cannot fully confirm if this is appropriate.

The following sentence is unclear: ‘According to the trends of each trajectory group, low stability, high stability, increase and decrease, and increasing were designated in men. In women, low stability, high stability and increasing groups were designated (Figure 2).’

In the text it could be clearer what each group means, i.e. ‘high stability’ means a high Fat to fat-free mass ratio without much variation between 1993 and 2009. Please clearly describe why fat to fat-free mass ratio was used and not just the fat % value?

Results

I’m concerned about the high number of individuals who fall into the ‘high stability’ group. I am not a statistician so I cannot say if this invalidates the statistical methods in any way. It would be worth having the analysis verified by a statistician.

What is the justification for the adjustment strategy in tables 4 and 5? Why not have an age adjusted model before adjustment for other confounders (education, marital status etc..)? For a better understanding of mediation by age or original weight status, these factors should be sequentially adjusted for in separate models.

In the conclusion the authors state ‘Our results also suggest that the impact of the adiposity trajectory on cardiometabolic profile is mediated by concurrent weight status.’ Is this a reference to tables 4 & 5 model 3? Could this association not also be mediated by age as age is included in model 3 along with weight status?

Figures 1 & 2: I can’t see the figure legends anywhere in the submitted manuscript? These should be provided.

Tables 2 & 3: the formatting is not quite right and makes the heading difficult to read.

Discussion

The discussion is not well written and as such it is quite hard to follow the discussion points. The findings are discussed fairly superficially, more insight into potential physiological underpinnings for the different F2MR trajectories is necessary. For example, why might the high-stability trajectory group be associated with hypertension in men, independent of concurrent age and weight status? There is repetition of statements throughout the discussion which is unnecessary.

Consider opening the discussion with a summary paragraph of the key results and why they are important/novel.

Paragraph 2: ‘dyslipidaemia was mainly affected by concurrent weight status’ I don’t think you can draw this conclusion without separating age/weight adjustment in model 3.

The limitation section should also include the high number of participants who fall into the low stability group and low numbers in the other groups and discussion of potential ethnic differences in body composition trajectories.

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6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

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Reviewer #1: No

Reviewer #2: No

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PONE-D-20-38516R1

Long-term Changes in Body Composition and their Relationships with Cardiometabolic Risk Factors: A Population-Based Cohort Study

PLOS ONE

Dear Dr. Liu,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by May 12 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Y Zhan

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: No

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: I Don't Know

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: The English language has largely been improved however I still do not think this paper is very well written. There are some outstanding and additional issues:

Introduction:

Line 45/46: “Millions of deaths can be ascribed to obesity worldwide[3], because it is associated with the development of cardiometabolic risk factors, such as dyslipidemia, diabetes, and hypertension[4, 5].”

This is not quite accurate. Dyslipidaemia, T2DM and hypertension are states of cardiometabolic disruption which increase the risk of adverse cardiovascular events.

Line 46/47: “Fat mass is used to evaluate obesity[6]”

In ref #6 they defined obesity using a BMI cut-off, so I don’t think this statement makes sense.

Line 61/62: “To date, few studies have characterized the trajectories of body composition and their associations with the development of cardiometabolic risk factors.”

I would say quite a large number of studies have tracked changes in body composition in longitudinal studies, however, I am unsure if this has previously been done in a Chinese population? Or if it has been done using the estimation of F2FFMR highlighting the importance of this work. Any more specific previous work on this should be referenced.

Methods:

(Q5&6) It is still not clear to me, from the written description and from Figure 1, how the authors arrived at the final sample size. What are the numbers in the box at the top right corner of fig 1?

“Those for whom data from at least two rounds of the survey were available were included.” How can you have a trajectory if you only have 2 measurements and such a wide age-range in this study sample? this should be explained, a supplementary information file might be helpful if the description is too lengthy for the main manuscript.

When were the cardiometabolic outcomes measured (at which visit)?

Was waist-hip ratio measured in this study?

(Q8) This is not true. Type 1 Diabetes develops in childhood but is still present into adulthood.

Results:

Table 5, statistically significant ORs not highlighted bold, as was done in Table 4.

Discussion:

Lines 247-250: “The effect of F2FFMR on cardiometabolic risk is likely to accumulate slowly, and high F2FFMR in early life might have an impact on cardiometabolic health in later life.”

It is not clear if these statements are based on evidence presented in previously published work? Or are speculation.

Line 256/256: “Study of the F2FFMR indicates that the adverse effects of high fat mass can be offset by the protective effects of high fat-free mass.”

Line 267/268: “The present findings also suggest that the impact of F2FFMR trajectory on cardiometabolic outcomes is mediated by changes in body mass.”

Is it ‘changes in body mass’ or just ‘current weight’? I think you should revise your interpretation of your results.

Line 270: do you mean the ‘high stability’ group or do you mean ‘highly stable’?

Line 294: I think the study sample from a Chinese only population living in China could be considered a strength of your study, given the previously published data from other parts of the world. There are other strengths that merit discussion as well.

Line299/300: “Our results also suggest that the association between F2FFMR trajectory and the cardiometabolic profile is mediated by body mass.”

If the associations are all mediated by current body mass status, then why do we need to know about the trajectories? It looks like your data do not fully support this statement: in women (table 5), dyslipidemia/diabetes/hypertension are all still higher in the ‘High Stability’ group despite adjustment for weight in 2009?

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Long-term Changes in Body Composition and their Relationships with Cardiometabolic Risk Factors: A Population-Based Cohort Study

PONE-D-20-38516R2

Dear Dr. Liu,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Y Zhan

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Partly

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: I Don't Know

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: No

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: The authors have addressed the comments sufficiently. The data is interesting and, to the best of my knowledge, the analysis is appropriate. English language used has been vastly improved however there are still small errors and places where the writing does not flow well. It is at the editors discretion whether these should be addressed.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No