PONE-D-25-38032Trends and Projections of the Global Burden of Type 2 Diabetic Nephropathy Related to High BMI: A Global Burden of Disease Study 2021PLOS ONE

Dear Dr. wang,

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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7. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 

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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: Partly

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

Reviewer #1: Yes

Reviewer #2: Yes

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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: Yes

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: The manuscript titled “Trends and Projections of the Global Burden of Type 2 Diabetic Nephropathy Related to High BMI: A Global Burden of Disease Study 2021” addresses an important and timely public health issue, using comprehensive GBD 2021 data to describe trends and make projections. The topic is relevant, the scope is global, and the statistical approaches (Joinpoint regression, decomposition analysis, Bayesian Age-Period-Cohort modeling) are appropriate. The manuscript is generally well-structured and clear, with a logical flow from introduction to discussion.

However, there are some methodological, interpretative, and presentation issues that should be addressed before the manuscript can be considered for publication.

Major Comments

1. Clarity on Data Sources and GBD Versions

The manuscript alternately refers to GBD 2021 and GBD 2024 data. This is confusing and should be clarified to avoid inconsistencies. If GBD 2024 updates were used, the title, abstract, and methods should reflect that clearly.

The authors should specify whether they used raw GBD estimates or age-standardized, modeled data from IHME, and how they handled missing or low-certainty data for some regions.

2. Definition of “High BMI”

The definition (>20–23 kg/m² depending on region) is unconventional, as most obesity-related research uses ≥25 kg/m² for overweight and ≥30 kg/m² for obesity in adults. This threshold should be justified, with clear reference to GBD’s operational definition and why it differs from WHO’s cut-offs.

3. Interpretation of Regional Trends

The discussion sometimes attributes differences solely to dietary habits or healthcare access without citing region-specific studies. While plausible, these interpretations would be stronger with region-specific epidemiological evidence.

The SDI-related trends (e.g., U-shaped relationships in low-to-middle SDI settings) deserve deeper exploration, potentially with supporting literature on health transition stages.

4. Projection Model Limitations

The Bayesian Age-Period-Cohort model assumes continuation of past trends. The manuscript should emphasize that public health interventions, new pharmacotherapies (e.g., GLP-1 receptor agonists, SGLT2 inhibitors), and socio-economic changes could substantially alter these projections.

The text should note explicitly that the model is not designed for short-term policy forecasting but for illustrating possible trajectories under status quo assumptions.

5. Sex Differences

The manuscript notes that men have higher ASMR/ASDR despite fewer absolute deaths than women. The discussion could benefit from integrating biological (e.g., fat distribution, hormonal effects) and socio-behavioral explanations, with literature support.

The widening gap between sexes over time should be contextualized with trends in obesity prevalence by sex.

6. Policy Implications

While the discussion suggests general interventions (diet, exercise, taxation), these remain broad. The paper could be strengthened by including specific examples of successful programs in high-burden regions, linked to the observed epidemiological patterns.

Minor Comments

1. Language and Style

The English is generally clear, but some sentences are overly long and would benefit from simplification for readability.

Certain terms should be standardized (e.g., “high body mass index” vs. “high BMI”).

2. Figures and Tables

Figure legends should be fully self-contained, describing abbreviations and clarifying that rates are age-standardized.

Consider including a supplementary table with country-level ASMR/ASDR values for transparency.

3. Referencing

Some statements in the discussion lack direct citations, especially those linking trends to dietary patterns or healthcare access.

References should be checked for format consistency with the journal’s style.

4. Ethics Statement

Although GBD data are publicly available, the ethics statement could note explicitly that no human participants were directly involved.

Recommendation:

Major Revision – The study is valuable and relevant, but revisions are needed to clarify definitions, ensure methodological transparency, strengthen the interpretation of results, and align discussion points more closely with evidence.

Reviewer #2: Dear Academic Editor,

Please find below my consolidated reviewer comments for the manuscript entitled “Trends and Projections of the Global Burden of Type 2 Diabetic Nephropathy Related to High BMI: A Global Burden of Disease Study 2021”.

This research manuscript explores the global burden of type 2 diabetic nephropathy (T2DN) associated with high body mass index (BMI), using data from the Global Burden of Disease (GBD) Study 2021. The study analyzes historical trends from 1990 to 2021 and projects scenarios through 2050, examining mortality and disability-adjusted life years (DALYs). It highlights that high BMI is an important driver of increasing T2DN, with notable regional and sex disparities. The research emphasizes the urgency of interventions to prevent obesity and to improve access to healthcare.

I would recommend a Major Revision focused on clarifying the manuscript’s novel contribution, strengthening the methodological justification, and improving precision in terminology (chronic kidney disease due to type 2 diabetes) and the BMI cut-points used. Implementing the suggested revisions would increase the manuscript’s clarity, reproducibility, and usefulness for policy-makers.

Context and novelty relative to recent studies

Why: Several recent GBD-based analyses address the burden of chronic kidney disease (CKD) attributable to type 2 diabetes and the role of high BMI (e.g., Wang et al., 2025 and others). Clarifying what is new in this manuscript will help readers and editors assess its added value.

Suggestion: The authors could add a brief paragraph in the Introduction that cites these recent studies and explains what the present manuscript adds (for example: projection horizon extended to 2050; an alternative projection method; more granular subregional/age/sex stratification; additional sensitivity analyses).

Clarify and justify the definition of “high BMI”

Why: Using thresholds such as 20–23 kg/m² labeled as “high BMI” can be confused with international categories for overweight/obesity (≥25/≥30 kg/m²). Interpreting results as “obesity-driven” without clarifying this distinction can be misleading.

Suggestion: The authors could clarify the exact source of these thresholds (e.g., GBD documentation, WHO Expert Consultation for Asian populations, or another reference), indicate which countries/regions apply which threshold (if applicable), and — where appropriate — use the term “elevated/high BMI” in Results and Conclusions instead of “obesity.”

Consistent terminology tied to the GBD definition (T2DM-Associated CKD / DKD)

Why: The term “diabetic nephropathy” usually implies clinical phenotypes (albuminuria, eGFR, KDIGO stages) that the GBD attributional category does not permit distinguishing. Using a neutral, explicit label avoids overinterpretation and is consistent with terminology adopted in other GBD-based works.

Suggestion: The authors could define and consistently use “T2DM-Associated CKD”, “CKD-T2DM” (or alternatively “Diabetic Kidney Disease, DKD” when used as a broad, non-phenotypic term). As noted in their Limitations (GBD does not distinguish proteinuria nor KDIGO stages), the Methods should state this explicitly.

Methodological details for reproducibility (Joinpoint, BAPC, code)

Why: Small modeling details influence replicability and the interpretation of projections.

Suggestion: The authors could provide methodological details in Methods: how data were imported into Joinpoint (R package or script), the maximum number of joinpoints allowed, the number of permutations used for permutation tests, significance thresholds, BAPC parameters (priors, MCMC iterations), software and package versions. If feasible, deposit analysis scripts in a public repository (e.g., GitHub, Zenodo) and provide the link.

Make the Data Availability Statement explicit

Why: Citing the GBD portal is helpful, but specifying the exact outputs improves reproducibility.

Suggestion: The authors could list the exact outputs extracted (deaths, DALYs, ASMR, ASDR), years, age groups, the cause definition used, and file formats. Providing the extracted dataset (CSV) as supplementary material would be useful.

Addressing these points would significantly improve the manuscript’s methodological transparency, terminological precision, and compliance with PLOS ONE’s style and reporting expectations.

Thank you for the opportunity to review this work.

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Reviewer #1: No

Reviewer #2: No

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Attachments

Attachment

Submitted filename: Review Comments to the Author.docx

PONE-D-25-38032R1Trends and Projections of the Global Burden of T2DM-Associated CKD Related to High BMI: A Global Burden of Disease Study 2021PLOS ONE

Dear Dr. wang,

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 Oct 23 2025 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: https://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,

Claudio Alberto Dávila-Cervantes, Ph.D.

Academic Editor

PLOS ONE

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If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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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 #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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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 #1: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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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 #1: Yes

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 #1: Yes

Reviewer #2: Yes

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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 #1: This is a timely and relevant analysis of the global burden of T2DM-associated CKD attributable to high BMI using GBD 2021 data. The projection horizon to 2050 and the stratification by sex, age, and SDI add clear value.

Strengths include comprehensive use of global data, improved terminology (“T2DM-associated CKD”), and region-specific discussion supported by epidemiological evidence.

Minor points for further improvement:

In the abstract/conclusions, highlight regional disparities and clarify that emerging therapies (GLP-1 RAs, SGLT2i) could alter future trajectories.

Ensure consistent use of terminology (“high BMI” vs. “obesity”; harmonize with GBD definitions).

Provide clarity on data availability (whether extracted CSV or repository link will be accessible).

Simplify long sentences to improve readability, and standardize abbreviations in figures/tables.

Add one more policy example from Asia or Africa to balance global representation.

Overall, this is a solid and well-revised manuscript; I recommend minor revisions to improve clarity and consistency.

This revised manuscript represents a substantial improvement and provides a valuable contribution to the literature on the global burden of T2DM-associated CKD attributable to high BMI. The use of GBD 2021 data, projections to 2050, and stratification by sex, age, and SDI add novelty and strengthen its public health relevance.

The authors have addressed the major reviewer concerns appropriately, including clarification of data sources, consistency of terminology, methodological transparency, and region-specific interpretation. The discussion is richer and includes relevant policy examples.

Remaining issues are minor: improving consistency of terminology (“high BMI” vs. “obesity”), ensuring clarity in the abstract/conclusions (particularly regarding regional disparities and the potential impact of emerging therapies), providing a clear data availability statement, and light language/formatting adjustments.

Reviewer #2: All comments have been addressed by the authors; thank you for the thorough revisions and attention to detail.

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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 #1: Yes:  Ana M Cebrián-Cuenca

Reviewer #2: Yes:  Juan Rodrigo Gómez-Bernal

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[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.

Trends and Projections of the Global Burden of T2DM-Associated CKD Related to High BMI: A Global Burden of Disease Study 2021

PONE-D-25-38032R2

Dear Dr. wang,

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.

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Kind regards,

Claudio Alberto Dávila-Cervantes, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: