Triglyceride-glucose index (TyG index) is associated with a higher risk of colorectal adenoma and multiple adenomas in asymptomatic subjects

Ziyue Zhu; Thomas Yuen Tung Lam; Raymond Shing Yan Tang; Sunny Hei Wong; Rashid Nok Shun Lui; Simon Siu Man Ng; Samuel Yeung Shan Wong; Joseph Jao Yiu Sung

doi:10.1371/journal.pone.0310526

Peer Review History

Original SubmissionMay 14, 2024
19 Aug 2024 Decision Letter - Fernando Guerrero-Romero, Editor PONE-D-24-18397Triglyceride-glucose index (TyG index) is associated with a higher risk of colorectal adenoma and multiple adenomas in asymptomatic subjects.PLOS ONE Dear Dr. Lam, 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. ============================== to:Thomas Yuen Tung Lam The manuscript you submitted (PONE-D-24-18397) was undergone external expert peer review and the first decision for your manuscript is: Minor changes. At this point, you must provide point-by-point responses to the comments raised by the Reviewers. ============================== Please submit your revised manuscript by Oct 03 2024 11:59PM. 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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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: I Don't Know Reviewer #2: Yes ****** 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). 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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 authors examine whether TgY Index is associated with risk of colorectal adenomas. They do a really nice job describing the statistical analysis methods used and where each method was used. Additionally, they do a good job with Tables 1-3. However, there is concern about the results sections labeled "Number of Adenoma" and "Subgroup Analysis". For number of adenoma, it is not clear how the analysis was done. The paragraph mentions that the number of adenomas is continuous in nature. This would imply possibly a linear regression model was created. However, there is no mention of such a technique being used in the statistical methods section. Additionally, Table 4 reports odds ratios, which are not the result of running a linear regression. Thus, it appears that number of adenomas was treated as something other than continuous. It should be explicitly stated how number of adenomas was treated (continuous, ordinal, binary) and exactly which type of model was created for this analysis. For the Subgroup analysis section, it is mentioned that both age and sex are found to be significant in the logistic and multinomial models. However, these results are not present anywhere else in the paper. It might be a good idea to add this information to the results presented in Tables 2 & 3 (and 4 if appropriate). This way, the reader can better follow along with the additional AOR's and see for themselves how the adjusted variables impact the results. The way the results of this section are presented appear different than the results of tables 2 & 3 (figure vs table). One style should be proposed for consistency. Additionally, it is not clear what is meant by " P for Interaction" from Figure 3. an interaction effect is usually one between two variables, and that does not appear to be what is presented. Clarification (or re-labeling) should be done for the p-value. Reviewer #2: The current manuscript represents a secondary analysis of two cohort studies that evaluated the availability of the TyG index to identify the presence of colorectal adenoma and multiple adenomas in asymptomatic subjects ≥50 years. In this regard, I have the following comments: For consistency, I suggest changing the study's hypothesis by the objective in the abstract. Figure 1 and its description should be moved to the Results section instead of Materials and Methods section. It would be useful to determine the sensitivity, specificity, and positive and negative predictive values of the TyG index for detecting both colorectal adenoma and multiple adenomas. Please add. ****** 6. 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Revision 1
25 Aug 2024 Author Response Response to Reviewers: Reviewer #1: The authors examine whether TgY Index is associated with risk of colorectal adenomas. They do a really nice job describing the statistical analysis methods used and where each method was used. Additionally, they do a good job with Tables 1-3. However, there is concern about the results sections labeled "Number of Adenoma" and "Subgroup Analysis". For number of adenoma, it is not clear how the analysis was done. The paragraph mentions that the number of adenomas is continuous in nature. This would imply possibly a linear regression model was created. However, there is no mention of such a technique being used in the statistical methods section. Additionally, Table 5 (originally Table 4) reports odds ratios, which are not the result of running a linear regression. Thus, it appears that number of adenomas was treated as something other than continuous. It should be explicitly stated how number of adenomas was treated (continuous, ordinal, binary) and exactly which type of model was created for this analysis. Thank you for your comments. We have added the following statement in “statistical analysis”: “For the estimations using number of adenomas as the endpoint, since we had a heavy tail distribution for the number of adenomas, we transformed the dependent variable onto the log scale and applied log-normal regression.” And we revised the design in abstract: “Its association with multiple adenomas (≥5) and the continuous number of adenomas were assessed by multinomial regression and log-normal linear regression, respectively.” All “log-normal estimation” or “log-normal regression” have been revised as “log-normal linear regression” for clarification. Table 4 reports estimates instead of odds ratios, as we stated in the “statistical analysis”: “The estimates would be interpreted as a percentage change in the number of adenomas.” For the Subgroup analysis section, it is mentioned that both age and sex are found to be significant in the logistic and multinomial models. However, these results are not present anywhere else in the paper. It might be a good idea to add this information to the results presented in Tables 2 & 3 (and 4 if appropriate). This way, the reader can better follow along with the additional AOR's and see for themselves how the adjusted variables impact the results. The way the results of this section are presented appear different than the results of tables 2 & 3 (figure vs table). One style should be proposed for consistency. Additionally, it is not clear what is meant by " P for Interaction" from Figure 3. an interaction effect is usually one between two variables, and that does not appear to be what is presented. Clarification (or re-labeling) should be done for the p-value. Thank you for your comments. The subgroup analysis for other endpoints has been added. The results are presented in the new Figure 3. “P for Interaction” was meant for the test for the age/gender interaction with TyG index. To avoid the confusion, this item has been removed from the Figure. The individual significance level can be seemed from the 95% confidence interval in Figure 3. Reviewer #2: The current manuscript represents a secondary analysis of two cohort studies that evaluated the availability of the TyG index to identify the presence of colorectal adenoma and multiple adenomas in asymptomatic subjects ≥50 years. In this regard, I have the following comments: For consistency, I suggest changing the study's hypothesis by the objective in the abstract. Thank you for your comments. The title “objective” has been replaced by “hypothesis” accordingly. Figure 1 and its description should be moved to the Results section instead of Materials and Methods section. Thank you for your comments. Figure 1 and its description have been moved to the “Results” section. It would be useful to determine the sensitivity, specificity, and positive and negative predictive values of the TyG index for detecting both colorectal adenoma and multiple adenomas. Please add. Thank you for your comments. Table 3 (Table 3. Sensitivity, specificity, PPV and NPV for detecting adenoma and multiple adenomas) and the corresponding discussion have been added to the manuscript. For adenoma detection: “The sensitivity, specificity, PPV and NPV of adenoma detection were presented in Table 3. Note that this model was not built for prediction and only aimed for showing the correlation between TyG index and risk of colorectal adenoma, and thus the values for sensitivity, specificity, PPV, and NPV were not sufficient to show enough discrimination power.” For multiple adenomas detection: “The sensitivity, specificity, PPV and NPV of multiple adenomas detection were presented in Table 3. Even though the confusion matrix showed insufficient discrimination power, the Multi-class AUC was 0.70, presenting an acceptable discrimination power.” Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0310526.r002
3 Sep 2024 Decision Letter - Fernando Guerrero-Romero, Editor Triglyceride-glucose index (TyG index) is associated with a higher risk of colorectal adenoma and multiple adenomas in asymptomatic subjects. PONE-D-24-18397R1 Dear Dr. Thomas Yuen Tung Lam 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. If you have any questions relating to publication charges, 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, Fernando Guerrero-Romero, MD, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): No additional comments Reviewers' comments: https://doi.org/10.1371/journal.pone.0310526.r003
Formally Accepted
16 Sep 2024 Acceptance Letter - Fernando Guerrero-Romero, Editor PONE-D-24-18397R1 PLOS ONE Dear Dr. Lam, 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 If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks 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. 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 Fernando Guerrero-Romero Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0310526.r004

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