Assessing the diagnostic accuracy of biochemical, anthropometric, and combined indices for metabolic syndrome prediction in a cohort from Qatar Biobank

Muhammad Ammar Zahid; Abrar Abdelrahman; Hicham Raïq; Abdelhamid Kerkadi; Abdelali Agouni

doi:10.1371/journal.pone.0339340

Peer Review History

Original SubmissionMarch 10, 2025
29 Sep 2025 Decision Letter - Amin Mansoori, Editor Dear Dr. Agouni, 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. ============================== Dear Author As you will note, three experts have reviewed the manuscript, and all have raised significant concerns regarding aspects such as the novelty, grammar, and other issues. Nevertheless, I believe the authors should be given the opportunity to revise the manuscript in response to the reviewers' comments. Best regards, Amin Mansoori ============================== Please submit your revised manuscript by Nov 13 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. 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, Amin Mansoori Academic Editor PLOS ONE Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. In the online submission form, you indicated that all relevant data are included within the manuscript. Additional data or information can be provided by the corresponding author upon reasonable request. All PLOS journals now require all data underlying the findings described in their manuscript to be freely available to other researchers, either 1. In a public repository, 2. Within the manuscript itself, or 3. Uploaded as supplementary information. This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. If your data cannot be made publicly available for ethical or legal reasons (e.g., public availability would compromise patient privacy), please explain your reasons on resubmission and your exemption request will be escalated for approval. 3. We note that you have indicated that there are restrictions to data sharing for this study. For studies involving human research participant data or other sensitive data, we encourage authors to share de-identified or anonymized data. However, when data cannot be publicly shared for ethical reasons, we allow authors to make their data sets available upon request. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Before we proceed with your manuscript, please address the following prompts: a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., a Research Ethics Committee or Institutional Review Board, etc.). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of recommended repositories, please see https://journals.plos.org/plosone/s/recommended-repositories. You also have the option of uploading the data as Supporting Information files, but we would recommend depositing data directly to a data repository if possible. Please update your Data Availability statement in the submission form accordingly. 4. Thank you for stating the following in the Acknowledgments Section of your manuscript: The study was funded by the Qatar National Research Fund (Qatar Research Development and Innovation Council) [grant No. NPRP14S-0406-210150] and Qatar University [grants No. QUST-1-CPH-2025-247 and QUST-2-CPH-2021-221]. M.A.Z. is supported by a Ph.D. graduate assistantship from the Office of Graduate Studies (Qatar University). The statements made herein are solely the responsibility of the authors. We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: The study was funded by the Qatar National Research Fund (Qatar Research Development and Innovation Council) [grant No. NPRP14S-0406-210150] and Qatar University [grants No. QUST-1-CPH-2025-247 and QUST-2-CPH-2021-221]. M.A.Z. is supported by a Ph.D. graduate assistantship from the Office of Graduate Studies (Qatar University). The statements made herein are solely the responsibility of the authors. Please include your amended statements within your cover letter; we will change the online submission form on your behalf. 5. Please amend either the abstract on the online submission form (via Edit Submission) or the abstract in the manuscript so that they are identical. 6. 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. Additional Editor Comments Dear Author As you will note, three experts have reviewed the manuscript, and all have raised significant concerns regarding aspects such as the novelty, grammar, and other issues. Nevertheless, I believe the authors should be given the opportunity to revise the manuscript in response to the reviewers' comments. Best regards, Amin Mansoori [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available??> The PLOS Data policy Reviewer #1: Yes Reviewer #2: No Reviewer #3: No ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes ****** Reviewer #1: Referee's opinion on the paper, “Assessing the diagnostic accuracy of biochemical, anthropometric, and combined indices for metabolic syndrome prediction in a cohort from Qatar Biobank” submitted in “PLOS ONE”. The manuscript investigated the comparison of the diagnostic accuracy of various indices for MetS prediction in QBB. The study was on 692 individuals and cross sectional. Authors used LR method to analyze the data. The methodology of the manuscript is enough however, I have some comments which are given as follows: 1- Introduction: Some sentences need references. For example, “Various criteria exist for diagnosing MetS, with the 2009 Harmonized Criteria being the most widely accepted.”, “A 2024 systematic review and meta-analysis reported an overall pooled prevalence of 26% in the Qatari population, with notable differences across age groups and diagnostic criteria.”, and … . 2- Introduction is not well-structured. It is so long and need to be shorten. 3- Abbreviation should be defined in first seen. Check whole paper in this regard. For example, QBB many times defined. 4- Do the data have any information about the medications of participants? It is an important factor related to MetS and Diabetes. 5- Discussion section needs more comparable explanation with literatures. For example, abdominal volume index (VAI) (10.3389/fcvm.2024.1341229, 10.1016/j.orcp.2021.10.001, 10.1038/s41371-023-00877-z, 10.1016/j.numecd.2021.04.024) is another index that can be compared or even adding in the analysis of the manuscript. 6- Recently, Cholesterol, High density lipoprotein, and Glucose (CHG) index (doi: 10.1111/jdi.14343) for T2DM was introduced that more efficient than TyG. I suggest adding this in your analysis. Reviewer #2: The manuscript “Assessing the diagnostic accuracy of biochemical, anthropometric, and combined indices for metabolic syndrome prediction in a cohort from Qatar Biobank” (PONE-D-25-08890) presents a well-conducted cross-sectional analysis that evaluates diagnostic indices for MetS in a Qatari cohort. The study addresses an important gap, given the high prevalence of metabolic risk factors in Qatar, and provides useful evidence on the comparative performance of biochemical, anthropometric, and combined indices. The study has several strengths: - The rationale and objectives are clearly presented, the sample size is adequate (n=692), and standardized IDF criteria were used. - The methodology is robust, employing logistic regression, ROC analysis, DeLong’s test, stratified analyses, and internal validation through a train-test split. - The reporting of results is clear, with tables and figures that effectively display comparisons across indices. - A key strength is the identification of LAP as the strongest predictor (AUC=0.896), with practical diagnostic thresholds that could be useful in clinical practice. At the same time, there are concerns that need to be addressed before the manuscript can be considered for publication. - The cross-sectional design restricts inference to associations at a single point in time. The manuscript should make clearer that the term “predictive performance” refers to discriminatory ability in a cross-sectional context, not prediction of future risk. - The representativeness of the Qatar Biobank sample is also an issue, since participants may not reflect the broader Qatari or regional population. This potential selection bias requires explicit discussion. - Another key issue is the clinical applicability of LAP and combined indices. Although they outperform traditional measures, the authors should explain whether these indices are easily calculated and practical for routine clinical use in Qatar. - The age-stratified results are noteworthy, showing markedly higher predictive accuracy in younger participants (<45 years). This important finding is not fully explored. The authors should discuss possible explanations, such as the higher prevalence of co-morbidities or confounding factors in older participants, and whether this limits generalizability of the indices to older adults. - The data availability statement also requires revision. PLOS ONE requires that data be openly accessible at the time of publication. The current phrasing (“available upon request”) is not compliant, and the authors should either deposit the data in a repository or provide a stronger justification for restrictions. Minor issues include: - Check for typographical errors (e.g., “Figurte S1”), also, some redundancy in the Introduction where the burden of MetS is repeated, and the need for clearer reporting of odds ratios. - Since continuous variables were standardized, this should be stated explicitly to aid interpretation. - Tables could also be simplified by merging overlapping content and providing clearer labeling for the combined indices. - The discussion could benefit from comparisons with similar regional studies beyond Qatar to highlight external validity. Overall, this is a strong and well-structured manuscript with clear clinical relevance. However, revisions are needed to strengthen the discussion of generalizability, clarify the implications of the age-stratified results, address clinical feasibility, and ensure compliance with data availability requirements. Therefore, I recommend major revision. Reviewer #3: This is a comprehensive manuscript that addresses a critical public health problem. However, the validity and interpretation of the results are difficult to assess due to a lack of clarity in the presentation. Many of the figures appear unclear, blurry, and ambiguous, which hinders the reader’s ability to interpret the data effectively. Additionally, I noticed some typographical errors, such as on line 155, which should be corrected. I recommend that the authors revise the manuscript for clarity, improve figure quality, and carefully proofread the text to enhance readability and ensure accurate communication of the findings. ****** 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: No Reviewer #2: Yes: Dalal Usamah Zaid Alkazemi Reviewer #3: 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. https://doi.org/10.1371/journal.pone.0339340.r001
Revision 1
7 Oct 2025 Author Response Point-by-Point Responses to the Editor and Reviewers’ Comments EDITOR / JOURNAL REQUIREMENTS 1. Ensure manuscript meets PLOS ONE style requirements. Response: Manuscript re-formatted per PLOS ONE style: section headings, figure/table numbering, and file naming have been standardized. 2 & 3. Data-availability compliance and justification. Response: The dataset is owned by Qatar Biobank (QBB) and contains identifiable participant data. Public release would breach MTA, NDA, and IRB terms and conditions. Inserted statement: “Data are available from Qatar Biobank under a controlled-access process and cannot be publicly shared due to IRB and data-transfer restrictions (IRB: Ex-2020-RES-ACC-0215-0125; Ex-2021-QF-QBB-RES-ACC-00049-0173). Requests should be directed to qphi@qf.org.qa.” 4. Funding statement placement. Response: The following text was retained only in the Funding Statement section and deleted from Acknowledgments: The study was funded by the Qatar National Research Fund (Qatar Research Development and Innovation Council) [grant No. NPRP14S-0406-210150] and Qatar University [grants No. QUT2RP-CPH-24/25-477, QUST-1-CPH-2025-247, and QUST-2-CPH-2021-221]. M.A.Z. is supported by a Ph.D. graduate assistantship from the Office of Graduate Studies (Qatar University). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 5. Abstract consistency. Response: Abstract on submission form and in manuscript now identical. 6. Evaluation of suggested literature. Response: All reference papers were reviewed, and relevant ones cited in the Discussion. REVIEWER #1 1. Missing references in the Introduction. Response: We have now included supporting citations for all unreferenced claims. 2. Introduction too long / restructure. Response: The section was condensed and reorganized for logical flow; redundant epidemiological detail was removed. 3. Abbreviations not defined at first appearance. Response: Full manuscript checked—each abbreviation defined at first use. 4. Medication data missing. Response: A lot of information on medication is missing in our dataset, so we could not, unfortunately, include this information in the analysis. 5. Discussion lacks a comparable explanation (VAI). Response: We have included a comparative discussion. The inserted paragraph includes: “The positive association between VAI and cardiometabolic disturbances observed in out cohort is consistent with the systematic review including 32 studies encompassing over 60,000 individuals across diverse age groups and regions, concluding that individuals with elevated VAI consistently exhibited higher blood pressure levels, independent of sex and age, underscoring VAI’s robustness as a marker of visceral adiposity and hemodynamic stress [49]. These findings reinforce our interpretation that VAI effectively captures the interplay between adipose tissue dysfunction and cardiometabolic risk. Complementary evidence from an Iranian population also highlighted the significance of VAI among adiposity indices. In their analysis of 9,704 adults from the MASHAD study, VAI remained significantly associated with hypertension in both men and women (OR = 1.03, 95% CI 1.02–1.04), even after adjustment for confounders [50]. Their findings reinforce the importance of VAI as a meaningful anthropometric indicator of blood pressure elevation and metabolic dysregulation across ethnic groups, supporting its inclusion in MetS risk assessment frameworks such as ours.” 6. Add CHG index. Response: The CHG index is now incorporated into methods, analysis, and results tables. We added the following line in the Introduction: “More recently Cholesterol, High-density lipoprotein, and Glucose (CHG) index have been used for the diagnosis of diabetes mellitus and is associated with MetS [19,20].” REVIEWER #2 1. Clarify that “predictive performance” refers to cross-sectional discrimination. Response: We replaced predictive-related terminology with “discriminatory ability/performance” throughout. 2. Representativeness of Qatar Biobank sample. Response: We added a limitation paragraph discussing QBB volunteer bias and limited generalizability. “A further limitation is the potential for selection bias. Participants in the Qatar Biobank are volunteers and may be healthier or more health-conscious than the general population. The cohort also predominantly comprises Qatari citizens, which may limit the generalizability of our findings to the large non-Qatari resident population in the country. Therefore, the prevalence and optimal thresholds of these indices should be validated in more diverse and representative community-based samples from Qatar and the wider Gulf region.” 3. Clinical applicability of LAP Response: We added a discussion paragraph as follows: “The clinical implementation of LAP is highly feasible, particularly in primary care settings. LAP requires only two common measurements: waist circumference, which is a simple anthropometric measure, and a fasting triglyceride level, which is part of a standard lipid panel. Given its simple calculation and high diagnostic accuracy demonstrated in our study, LAP and VAI represent a cost-effective and powerful tool that can be easily integrated into routine health check-ups in Qatar to improve early detection of MetS.” 4. Age-stratified results. Response: We added an explanation for stronger performance in younger participants as follows: “A particularly noteworthy finding from our study was the significantly higher discriminatory ability of all indices in individuals younger than 45 years. This age-related difference may be attributable to several factors. In older adults (≥45 years), the metabolic landscape is often complicated by a higher prevalence of comorbidities and the use of medications (e.g., statins, antihypertensives), which can alter lipid and glucose levels, thereby reducing the diagnostic clarity of these indices. Furthermore, physiological changes associated with aging, such as alterations in body composition and fat distribution, might weaken the association between these surrogate markers and MetS. This finding suggests that while these indices are exceptionally useful for identifying at-risk younger adults, their interpretation in older populations may require greater clinical nuance and consideration of confounding factors.” 5. Data-availability revision. Response: We updated the statement as follows: “Data are available from Qatar Biobank under a controlled-access process and cannot be publicly shared due to IRB and data-transfer restrictions (IRB: Ex-2020-RES-ACC-0215-0125; Ex-2021-QF-QBB-RES-ACC-00049-0173). Requests should be directed to qphi@qf.org.qa.” 6. Typographical and redundancy corrections. Response: All typos have been corrected, and redundant statements have been removed. 7. Continuous variables standardized. Response: We added the following statement to the Methods: “For the logistic regression analysis, all continuous variables were standardized (converted to z-scores) to allow for the comparison of odds ratios across different measures.” 8. Simplify tables / clarify labels. Response: We included abbreviation footnotes and uniform labeling for all tables. REVIEWER #3 1. Figures unclear/blurry. Response: We replaced those figures with high-resolution versions in corrected aspect ratios. All relevant information is also presented in the associated tables. 2. Typographical errors. Response: We proofread the entire text; all typographical issues were now corrected. Attachments Attachment Submitted filename: PLOS_ONE_Rebuttal.docx https://doi.org/10.1371/journal.pone.0339340.r002
26 Oct 2025 Decision Letter - Amin Mansoori, Editor Dear Dr. Agouni, 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 Dec 10 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. 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 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, Amin Mansoori Academic Editor PLOS ONE Journal Requirements: 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. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author Reviewer #2: All comments have been addressed Reviewer #3: (No Response) ******** 2. Is the manuscript technically sound, and do the data support the conclusions??> Reviewer #2: Yes Reviewer #3: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #2: Yes Reviewer #3: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available??> The PLOS Data policy Reviewer #2: Yes Reviewer #3: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #2: Yes Reviewer #3: Yes ****** Reviewer #2: The authors added the CHG index, improved the Introduction, clarified terminology, added missing references, and corrected tables and figures. Discussion sections now include comparisons for VAI and LAP, along with explanations of age effects and clinical relevance. The manuscript is clear, complete, and ready for acceptance. Reviewer #3: The figures are hard to read and correlate to the note written. Can the figures be made more readable? Also, why not have the figures where the legend is located just like the tables? That would make the reading flow better even for reviewers. ****** 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: Yes: Dalal Usamah Zaid Alkazemi Reviewer #3: 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.] To ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures You may also use PLOS’s free figure tool, NAAS, to help you prepare publication quality figures: https://journals.plos.org/plosone/s/figures#loc-tools-for-figure-preparation. NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications. https://doi.org/10.1371/journal.pone.0339340.r003
Revision 2
29 Oct 2025 Author Response REVIEWER #3 1. The figures are hard to read and correlate to the note written. Can the figures be made more readable? Also, why not have the figures where the legend is located just like the tables? That would make the reading flow better even for reviewers. Response: We thank the reviewer for their feedback. We have addressed the two points as follows: • Figure Readability: This issue has been fully resolved. We have replaced all figures with high-resolution versions, ensuring each one complies strictly with the journal’s technical specifications, including a minimum resolution of 300 DPI and adherence to the maximum dimensions of 7.5 x 8.25 inches. The revised figures are now crisp, clear, and fully legible. • Figure Placement: Regarding the suggestion to embed figures within the text alongside their captions, this request is in direct conflict with PLOS ONE's mandatory author guidelines. The journal's formatting policy explicitly requires authors to submit figure files separately and not to embed them in the manuscript file. The guidelines state that captions must be listed in the manuscript text after the first paragraph of their citation. Accordingly, we have strictly adhered to the journal’s submission protocol. To do otherwise would be a direct violation of the submission requirements. We are confident that with the vastly improved resolution, correlating the figures with their corresponding captions in the text is now straightforward. We trust this clarifies why we could not accommodate this specific suggestion and confirms our compliance with the journal's formatting standards. Attachments Attachment Submitted filename: PLOS_ONE_Rebuttal_auresp_2.docx https://doi.org/10.1371/journal.pone.0339340.r004
7 Dec 2025 Decision Letter - Marwan Salih Al-Nimer, Editor Assessing the diagnostic accuracy of biochemical, anthropometric, and combined indices for metabolic syndrome prediction in a cohort from Qatar Biobank PONE-D-25-08890R2 Dear Dr. Abdelali Agouni, 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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support . 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, Marwan Salih Al-Nimer, MD, PhD Academic Editor PLOS One Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author Reviewer #2: All comments have been addressed Reviewer #4: (No Response) ******** 2. Is the manuscript technically sound, and do the data support the conclusions??> Reviewer #2: Yes Reviewer #4: No ****** 3. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #2: Yes Reviewer #4: No ****** 4. Have the authors made all data underlying the findings in their manuscript fully available??> The PLOS Data policy Reviewer #2: Yes Reviewer #4: No ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #2: Yes Reviewer #4: No ****** Reviewer #2: - Explicitly state whether all models were adjusted for potential confounders such as age and smoking. If not adjusted, note this as a limitation. Reviewer #4: The authors investigate the association and diagnostic performance of biochemical, anthropometric, and composite indices for predicting metabolic syndrome. Their findings show that variables such as fasting glucose, HbA1c, triglycerides, HDL-C, waist circumference, BMI, and several derived indices are associated with metabolic syndrome and can discriminate individuals with and without the condition. However, a fundamental conceptual issue arises: several of these parameters—specifically waist circumference, triglycerides, HDL-C, and glucose—are themselves diagnostic components of metabolic syndrome according to widely adopted criteria (e.g., NCEP ATP III, IDF). Evaluating the association or predictive accuracy of variables that directly define the condition introduces circular reasoning. Demonstrating that diagnostic criteria predict the diagnosis they determine does not add scientific value and risks overstating the novelty or clinical utility of the findings. The authors should explicitly justify why these analyses were performed, clarify the intended incremental value beyond the known diagnostic components, and consider focusing on indices or biomarkers that are not part of the defining criteria of metabolic syndrome. Without this clarification, the study’s conclusions may be interpreted as tautological rather than informative. ****** 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: Yes: Dr. Dalal Usamah Zaid Alkazemi Reviewer #4: No ******** https://doi.org/10.1371/journal.pone.0339340.r005
Formally Accepted
Acceptance Letter - Marwan Salih Al-Nimer, Editor PONE-D-25-08890R2 PLOS One Dear Dr. Agouni, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS One. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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. You will receive an invoice from PLOS for your publication fee after your manuscript has reached the completed accept phase. If you receive an email requesting payment before acceptance or for any other service, this may be a phishing scheme. Learn how to identify phishing emails and protect your accounts at https://explore.plos.org/phishing. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Professor Marwan Salih Al-Nimer Academic Editor PLOS One https://doi.org/10.1371/journal.pone.0339340.r006

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .