Association between triglyceride-glucose derived indices with cardiometabolic multimorbidity: Findings from the Atherosclerosis Risk in Communities study

Yi Liu; Dongze Li; Jing Yu; Yongli Gao; Wei Zhang; Menglin Tang

doi:10.1371/journal.pone.0339646

Peer Review History

Original SubmissionApril 26, 2025
17 Nov 2025 Decision Letter - Alessandro Cannavo, Editor 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 Jan 01 2026 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'. 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We look forward to receiving your revised manuscript. Kind regards, Alessandro Cannavo 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. Thank you for uploading your study's underlying data set. Unfortunately, the repository you have noted in your Data Availability statement does not qualify as an acceptable data repository according to PLOS's standards. At this time, please upload the minimal data set necessary to replicate your study's findings to a stable, public repository (such as figshare or Dryad) and provide us with the relevant URLs, DOIs, or accession numbers that may be used to access these data. For a list of recommended repositories and additional information on PLOS standards for data deposition, please see https://journals.plos.org/plosone/s/recommended-repositories . 3. Please ensure that you refer to Figure 1 in your text as, if accepted, production will need this reference to link the reader to the figure. 4. 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. 5. 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.] 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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #1: Yes Reviewer #2: 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: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: Yes Reviewer #2: Yes ****** Reviewer #1: Cardiometabolic multimorbidity (CMM) represents a major public health challenge in the context of an aging population. This study moves beyond the conventional single-disease research framework by focusing on the complex co-occurrence of diabetes mellitus (DM), coronary heart disease (CHD), and stroke, thereby aligning with contemporary advances in precision prevention and integrative medicine. Drawing on the well-established Atherosclerosis Risk in Communities (ARIC) cohort, the research benefits from a large sample size (n = 12,450), an extended follow-up period, and high-quality longitudinal data, all of which contribute to the robustness and scientific validity of the findings. The article features a clear organizational structure, a sound study design, rigorous statistical methodology, and conclusions that carry meaningful clinical implications.However, the following two suggestions are proposed to further strengthen the manuscript: 1. Objective interpretation of predictive efficacy: The article identifies TyG-BMI as the indicator with the strongest discriminatory ability (AUC = 0.684; 95% CI: 0.664–0.705). While this represents the highest performance among the compared indices, the AUC value remains within the "moderate" range of discrimination, as an AUC above 0.7 is typically considered indicative of good discriminatory power. Therefore, relying solely on TyG-BMI for clinical screening may be suboptimal. It is recommended that the discussion section provide a more balanced assessment of its clinical utility, positioning TyG-BMI as a potential tool for initial screening or risk stratification rather than as an independent diagnostic criterion, thereby avoiding potential overestimation of its applicability in clinical practice. 2. Enhancement of clinical operability: To improve the translational relevance of the findings, it is suggested that a nomogram incorporating TyG-BMI and other significant predictors be included in the supplementary materials. Such a tool would enable clinicians to perform individualized prediction of CMM risk in a more intuitive and practical manner, thereby increasing the clinical applicability and impact of the study. Reviewer #2: 1. The manuscription is written fairly well but can benefit from a final language editing. 2. The authors have clarified the data presented and how it was analysed. 3. The objective should be specific and state the actual variables tested for associations (please replace "their" with the actual variable of interest, e.g : the association of TyG, TyG-BMI, TyG-WC, and TyG-WHtR with...... 4. Authors should include the models highlighted in Table 2, in the methodology first. ****** 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: Prof. Nombeko Mshunqane ******** [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. Attachments Attachment Submitted filename: manuscript (2).docx https://doi.org/10.1371/journal.pone.0339646.r001
Revision 1
20 Nov 2025 Author Response November _20, 2025 Emily Chenette Editor-in-Chief PLOS ONE Manuscript ID: PONE-D-25-21918 Manuscript title: Association between triglyceride-glucose–derived indices with cardiometabolic multimorbidity: Findings from the Atherosclerosis Risk in Communities study Dear editor: We thank you and the reviewers for reviewing our manuscript and for providing valuable comments. We have revised the manuscript according to the comments. Our responses to the comments are provided below. We look forward to working with you and the reviewers to move this manuscript closer to publication Thank you for your consideration. We look forward to hearing from you. Sincerely, Prof. Menglin Tang, BS Department of Cardiac Surgery, West China Hospital, Sichuan University, 37 Guoxue Road, Chengdu 610041, Sichuan, China. Tel: +86-28-85422461, Fax: +86-28-85422288 E-mail: menglin_tang@163.com Journal 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 Thanks for your comment. The manuscript has been formatted per PLOS ONE style requirements. 2. Thank you for uploading your study's underlying data set. Unfortunately, the repository you have noted in your Data Availability statement does not qualify as an acceptable data repository according to PLOS's standards. At this time, please upload the minimal data set necessary to replicate your study's findings to a stable, public repository (such as figshare or Dryad) and provide us with the relevant URLs, DOIs, or accession numbers that may be used to access these data. For a list of recommended repositories and additional information on PLOS standards for data deposition, please see https://journals.plos.org/plosone/s/recommended-repositories. The data from the ARIC study are not freely available as it would compromise the privacy of the study participants, particularly because the data include sensitive health information. Data can be requested through the Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) website (https://biolincc.nhlbi.nih.gov/studies/aric/) after creating an account and registering at the site. The data dictionary is available on this website. More information about the ARIC study can be found at https://aric.cscc.unc.edu/aric9/. 3. Please ensure that you refer to Figure 1 in your text as, if accepted, production will need this reference to link the reader to the figure. We thank you for pointing this out. We have cited Figure 1 in the subsection “Study design and population” in page 5. This analytical cohort utilized visit 1 as the baseline reference, incorporating all 15,792 initially enrolled subjects. Individuals with pre-existing CHD, stroke, or DM (n = 2,799) and those with incomplete covariate data (n = 543) were excluded from the analysis. Thus, the final analytical cohort consisted of 12,450 participants (Fig 1). 4. 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. Thanks for your reminder. The reviewers' comments do not include such suggestions. 5.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. We thank you for this important reminder. We have thoroughly reviewed the reference list and confirmed its completeness and accuracy. All references have been checked against their original sources and any formatting inconsistencies have been corrected to ensure full compliance with the journal's style guide. We confirm that none of the cited papers have been retracted. Reviewer #1: Cardiometabolic multimorbidity (CMM) represents a major public health challenge in the context of an aging population. This study moves beyond the conventional single-disease research framework by focusing on the complex co-occurrence of diabetes mellitus (DM), coronary heart disease (CHD), and stroke, thereby aligning with contemporary advances in precision prevention and integrative medicine. Drawing on the well-established Atherosclerosis Risk in Communities (ARIC) cohort, the research benefits from a large sample size (n = 12,450), an extended follow-up period, and high-quality longitudinal data, all of which contribute to the robustness and scientific validity of the findings. The article features a clear organizational structure, a sound study design, rigorous statistical methodology, and conclusions that carry meaningful clinical implications.However, the following two suggestions are proposed to further strengthen the manuscript: 1.Objective interpretation of predictive efficacy: The article identifies TyG-BMI as the indicator with the strongest discriminatory ability (AUC = 0.684; 95% CI: 0.664–0.705). While this represents the highest performance among the compared indices, the AUC value remains within the "moderate" range of discrimination, as an AUC above 0.7 is typically considered indicative of good discriminatory power. Therefore, relying solely on TyG-BMI for clinical screening may be suboptimal. It is recommended that the discussion section provide a more balanced assessment of its clinical utility, positioning TyG-BMI as a potential tool for initial screening or risk stratification rather than as an independent diagnostic criterion, thereby avoiding potential overestimation of its applicability in clinical practice. We thank you for this insightful comment and agree that there is a need for a balanced interpretation of the predictive efficacy of TyG-BMI. As you pointed out, an AUC of 0.684 falls within the “moderate” range of discrimination. Following the suggestion, we have revised the Discussion as follows: It is noteworthy that although TyG-BMI demonstrated the strongest discriminatory ability among the evaluated indices, its AUC value was 0.684 (95% CI: 0.664–0.705), which is generally considered to represent "moderate" accuracy. Consequently, the clinical value of TyG-BMI may not lie in its potential as a diagnostic tool, but as a simple and inexpensive tool for early risk identification or risk stratification in patients with CMM. 2.Enhancement of clinical operability: To improve the translational relevance of the findings, it is suggested that a nomogram incorporating TyG-BMI and other significant predictors be included in the supplementary materials. Such a tool would enable clinicians to perform individualized prediction of CMM risk in a more intuitive and practical manner, thereby increasing the clinical applicability and impact of the study. We thank you for this excellent suggestion to enhance the clinical applicability of our findings. Accordingly, we have developed a clinically applicable nomogram that integrates TyG-BMI with other significant independent predictors identified in our multivariate analysis for the individualized prediction of CMM risk. This nomogram has been included as Supplementary Figure S1 and the corresponding description has been provided in the Results. We believe that this visual tool will greatly facilitate the translation of our research into clinical practice by allowing for intuitive risk estimation. The nomogram in S1 Fig depicts the predicted probability of CMM using TyG-BMI, measured on a scale of 0 to 130. Reviewer #2: 1.The manuscription is written fairly well but can benefit from a final language editing. Thank you for your comment. The revised manuscript has be checked by a Language Editing service provider. 2.The objective should be specific and state the actual variables tested for associations (please replace "their" with the actual variable of interest, e.g : the association of TyG, TyG-BMI, TyG-WC, and TyG-WHtR with...... Thank you for your careful review. We have revised the sentence as follows: Our objective was to investigate the association of TyG, TyG-BMI, TyG-WC, and TyG-WHtR with incident CMM; identify the optimal predictive biomarker for this complex multimorbidity phenotype; and offer actionable strategies for early CMM risk stratification. 3. Authors should include the models highlighted in Table 2, in the methodology first We thank you for this suggestion. We have revised the subsection Statistical analysis to include a detailed description of the models highlighted in Table 2. This revision provides the necessary theoretical foundation before the results are presented in the table. The regression model gradually adjusted for the potential confounding factors in three levels. Model 1 did not adjust for variables. Model 2 adjusted for demographic characteristics (sex, ethnicity, and age) and history of hypertension. Model 3 further adjusted for lifestyle factors (drinking and smoking status) and clinical biomarkers (total cholesterol, HDL, LDL, and triglyceride levels) on the basis of Model 2. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0339646.r002
9 Dec 2025 Decision Letter - Alessandro Cannavo, Editor Association between triglyceride-glucose derived indices with cardiometabolic multimorbidity: Findings from the Atherosclerosis Risk in Communities study PONE-D-25-21918R1 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 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, Alessandro Cannavo Academic Editor PLOS One Reviewers' comments: Reviewer's Responses to Questions Comments to the Author Reviewer #1: (No Response) Reviewer #2: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions??> Reviewer #1: (No Response) Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #1: (No Response) Reviewer #2: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available??> The PLOS Data policy Reviewer #1: (No Response) Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: (No Response) Reviewer #2: Yes ****** Reviewer #1: (No Response) Reviewer #2: The authors have addressed all reviewer's comments and those for reviewer 1. Where they did not make corrections as recommended by reviewers, a detailed reason is supplied. I Accept the manuscript for publication. ****** 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: No ******** https://doi.org/10.1371/journal.pone.0339646.r003
Formally Accepted
Acceptance Letter - Alessandro Cannavo, Editor PONE-D-25-21918R1 PLOS One Dear Dr. Liu, 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 Dr. Alessandro Cannavo Academic Editor PLOS One https://doi.org/10.1371/journal.pone.0339646.r004

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