Utility of Fatty Liver Index to predict reversion to normoglycemia in people with prediabetes

Carla Busquets-Cortés; Miquel Bennasar-Veny; Ángel Arturo López-González; Sergio Fresneda; Manuela Abbate; Aina M. Yáñez

doi:10.1371/journal.pone.0249221

Peer Review History

Original SubmissionDecember 10, 2020
11 Feb 2021 Decision Letter - Michael W Greene, Editor PONE-D-20-38894 Utility of Fatty Liver Index to predict reversion to normoglycemia in people with prediabetes PLOS ONE Dear Dr. Bennasar-Veny, 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. There is currently unprecedented pressure on reviewers. As such, I have been unable to obtain a timely second review of your manuscript. However, I have received a thoughtful, detailed review which can guide you in the revision of your manuscript. I agree with the reviewers comments. Please submit your revised manuscript by March 26, 2021. 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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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: 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). 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 ****** 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 ****** 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: This is a well-designed observational prospective study about well-defined clinical question, the reversion of prediabetes according to baseline FLI levels. The article is well structured and written, so I have no major objections, except that perhaps some comments should be made in the introduction, or even in the discussion, on the results of a previous study published in 2018 in PlosOne referring to a Spanish primary care population (The PREDAPS study): Franch-Nadal J, Caballeria L, Mata-Cases M, Mauricio D, Giraldez-García C, Mancera J, Goday A, Mundet-Tudurí X, Regidor E; PREDAPS Study Group. Fatty liver index isa predictor of incident diabetes in patients with prediabetes: The PREDAPS study. PLoS One. 2018 Jun 1;13(6):e0198327. doi: 10.1371/journal.pone.0198327. eCollection 2018. In relation to the limitations of the study, it is worth mentioning the lack of HbA1c values, which is one of the diagnoses of prediabetes criteria (ADA) and due to its lower variability than Fasting Plasma Glucose is a more precise tool for diagnosis. Moreover, the fact that only one measurement of Fasting Plasma Glucose was available reduces accuracy of the diagnosis and precludes the exclusion of patients with an isolated elevated value that would disappear due to the regression-to-the-mean effect. I think that this limitation needs to be mentioned to a greater extent in the discussion. Additionally, there are some minor corrections or suggestions that are detailed below. Minor changes/corrections or suggestions Abstract 1. Page 8 (lines 39): To homogenize with other OR values, add the third decimal: 1.544 Introduction: 2. page 10, line 86: Refer or add a short comment on the reference I have mentioned before (PREDAPS study). 3. Page 13, line 151. Correct NALF, it has to be NAFLD Results: 4. Page 11, Table 1. There is an error on the WC line WC (cm) 44.2 ± 53.7 88.9 ± 9.7 83.2 ± 9.2 < 0.001 Obviously, the mean of WC for all patients (44.2) must be between 83 and 89 cm. Note that the DE is also wrong and should be between 9.2 and 9.7 5. Page 16, line 220: To homogenize with other OR values, add the third decimal: 1.544 6. Page 18, lines 238-239 Remove the title of the figure as it is already at the end of de main text. Discussion: 7. Page 20, line 301: I think that the limitations I suggested before (lack of HbA1c values and only one measurement of FPG) need to be commented to a greater extent here. An HbA1c between 5.7 and 6.4% is one of the criteria for the diagnoses of prediabetes (ADA) and due to its lower variability than Fasting Plasma Glucose is a more precise tool for diagnosis. Moreover, the fact that only one measurement of Fasting Plasma Glucose was available reduces accuracy of the diagnosis and precludes the exclusion of patients with an isolated elevated value that would disappear due to the regression-to-the-mean effect. 8. Page 13, line 20. Please, consider to add a comment or comparison with the results of the reference I have suggested before (the PREDAPS study) Conclusions 9. The conclusions section does not literally correspond to the sentences included in the conclusions in the abstract. It must be homogenized, adding the phrases included in the abstract in this section. 10. Moreover, one of the sentences (Pag 20, line 307) is difficult to understand and has to be modified: “Since NAFLD is a risk factor for the development of T2D, a reduced risk of presenting hepatic steatosis may increase the chances of reverting from prediabetes to normoglycemia…” The authors cannot speculate about the reduction of the risk of hepatic steatosis on the reversion of prediabetes… So, I suggest to change the “a reduced risk of presenting” for “the absence of” or something like that. References Please add the PREDAPS study reference and complete or correct the following references: 11. Pag 21, line 332: remove prediabetes at the end of the ref 12. Pag 22, line 335: it has to be: BMJ. 2016 Nov 23;355:i5953. doi: 10.1136/bmj.i5953. 13. Pag 22, line 351: it has to be: Int. J. Environ. Res. Public Health 2019, 16, 3104; doi:10.3390/ijerph16173104 14. Pag 25, line 457: it has to be corrected and completed: Beta-cell function in obesity: effects of weight loss. Diabetes 2004 Dec;53 Suppl 3:S26-33. doi: 10.2337/diabetes.53.suppl_3.s26. In summary, I want to congratulate the authors for the quality of the article. Finally, some comments in the discussion as I have suggested could be of great interest and well received. ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. 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 [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.0249221.r001
Revision 1
21 Feb 2021 Author Response Responses to reviewers: Reviewer #1: This is a well-designed observational prospective study about well-defined clinical question, the reversion of prediabetes according to baseline FLI levels. The article is well structured and written, so I have no major objections, except that perhaps some comments should be made in the introduction, or even in the discussion, on the results of a previous study published in 2018 in PlosOne referring to a Spanish primary care population (The PREDAPS study): Franch-Nadal J, Caballeria L, Mata-Cases M, Mauricio D, Giraldez-García C, Mancera J, Goday A, Mundet-Tudurí X, Regidor E; PREDAPS Study Group. Fatty liver index isa predictor of incident diabetes in patients with prediabetes: The PREDAPS study. PLoSOne. 2018 Jun 1;13(6):e0198327. doi: 10.1371/journal.pone.0198327. eCollection 2018. In relation to the limitations of the study, it is worth mentioning the lack of HbA1c values, which is one of the diagnoses of prediabetes criteria (ADA) and due to its lower variability than Fasting Plasma Glucose is a more precise tool for diagnosis. Moreover, the fact that only one measurement of Fasting Plasma Glucose was available reduces accuracy of the diagnosis and precludes the exclusion of patients with an isolated elevated value that would disappear due to the regression-to-the-mean effect. I think that this limitation needs to be mentioned to a greater extent in the discussion. Additionally, there are some minor corrections or suggestions that are detailed below. Minor changes/corrections or suggestions Abstract 1. Page 8 (lines 39): To homogenize with other OR values, add the third decimal: 1.544. R: We thank the reviewer for pointing out the mistake. We have now replaced 1.54 with 1.544 in the abstract. Introduction: 2. page 10, line 86: Refer or add a short comment on the reference I have mentioned before (PREDAPS study). R: We thank the referee for the useful suggestion. We have commented in the introduction results from the article mentioned. 3. Page 13, line 151. Correct NALF, it has to be NAFLD. R: We have corrected the typo. Results: 4. Page 11, Table 1. There is an error on the WC line WC (cm) 44.2 ± 53.7 88.9 ± 9.7 83.2 ± 9.2 < 0.001. Obviously, the mean of WC for all patients (44.2) must be between 83 and 89 cm. Note that the DE is also wrong and should be between 9.2 and 9.7. R: We are grateful to the reviewer for pointing out this inaccuracy, and we have replaced the mistaken information with correct data. 5. Page 16, line 220: To homogenize with other OR values, add the third decimal: 1.544. R: We have replaced 1.54 with 1.544 in the results, according to the reviewer’s suggestion. 6. Page 18, lines 238-239 Remove the title of the figure as it is already at the end of de main text. R: We removed the title of the figure within the text, as it is at the end of the main text. Discussion: 7. Page 20, line 301: I think that the limitations I suggested before (lack of HbA1c values and only one measurement of FPG) need to be commented to a greater extent here. An HbA1c between 5.7 and 6.4% is one of the criteria for the diagnoses of prediabetes (ADA) and due to its lower variability than Fasting Plasma Glucose is a more precise tool for diagnosis. Moreover, the fact that only one measurement of Fasting Plasma Glucose was available reduces accuracy of the diagnosis and precludes the exclusion of patients with an isolated elevated value that would disappear due to the regression-to-the-mean effect. R: We thank the reviewer for the comment. We agree that HbA1c has a lower variability that Fasting Plasma Glucose (FPG), however, as now explained as a limitation, this variable was not collected for all subjects. The study sample includes data from occupational routine health assessments, during which HbA1c measurements are done on workers with previously identified elevated FPG. We also agree with the fact that with only one measurement of FPG available, the possibility to regression toward the mean phenomenon can take place, thus possibly affecting the regression rate. We included such limitation in the text. 8. Page 13, line 20. Please, consider to add a comment or comparison with the results of the reference I have suggested before (the PREDAPS study). R: We thank the referee for the useful suggestion. We have commented in the discussion results from the article mentioned. Conclusions: 9. The conclusions section does not literally correspond to the sentences included in the conclusions in the abstract. It must be homogenized, adding the phrases included in the abstract in this section. R: We thank the reviewer for the valuable comment. Accordingly, we have modified the conclusion within the text in order to homogenize it with the conclusions in the abstract. 10. Moreover, one of the sentences (Pag 20, line 307) is difficult to understand and has to be modified: “Since NAFLD is a risk factor for the development of T2D, a reduced risk of presenting hepatic steatosis may increase the chances of reverting from prediabetes to normoglycemia…” The authors cannot speculate about the reduction of the risk of hepatic steatosis on the reversion of prediabetes… So, I suggest to change the “a reduced risk of presenting” for “the absence of” or something like that. R: We agree with the reviewer comment. We removed “a reduced risk of presenting” and wrote “the absence of” instead. References Please add the PREDAPS study reference and complete or correct the following references: 11. Pag 21, line 332: remove prediabetes at the end of the ref. R: Thank you for pointing out the mistake. We removed the word “prediabetes” at the end of the reference. 12. Pag 22, line 335: it has to be: BMJ. 2016 Nov 23;355: i5953. doi: 10.1136/bmj.i5953. R: We have corrected the reference. 13. Pag 22, line 351: it has to be: Int. J. Environ. Res. Public Health 2019, 16, 3104; doi:10.3390/ijerph16173104. R: We have added the missing information. 14. Pag 25, line 457: it has to be corrected and completed: Beta-cell function in obesity: effects of weight loss. Diabetes 2004 Dec;53 Suppl 3:S26-33. doi: 10.2337/diabetes.53.suppl_3.s26. R: We have completed the information. The title was missing due to an error with our cite-o-matic system. In summary, I want to congratulate the authors for the quality of the article. Finally, some comments in the discussion as I have suggested could be of great interest and well received. R: We thank the reviewer for the kind comments and for giving us the opportunity to revisit the manuscript while taking into consideration the comments made. Attachments Attachment Submitted filename: Response to reviewers.docx https://doi.org/10.1371/journal.pone.0249221.r002
15 Mar 2021 Decision Letter - Michael W Greene, Editor Utility of Fatty Liver Index to predict reversion to normoglycemia in people with prediabetes PONE-D-20-38894R1 Dear Dr. Bennasar-Veny, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Michael W Greene, Ph.D. Academic Editor PLOS ONE 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 ******** 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 ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes ****** 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 ****** 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 ****** 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: (No Response) ****** 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: No https://doi.org/10.1371/journal.pone.0249221.r003
Formally Accepted
19 Mar 2021 Acceptance Letter - Michael W Greene, Editor PONE-D-20-38894R1 Utility of Fatty Liver Index to predict reversion to normoglycemia in people with prediabetes. Dear Dr. Bennasar-Veny: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. 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 plosone@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. Michael W Greene Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0249221.r004

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