Safety and efficacy of very low carbohydrate diet in patients with diabetic kidney disease—A randomized controlled trial

Nur Aisyah Zainordin; Nur’ Aini Eddy Warman; Aimi Fadilah Mohamad; Fatin Aqilah Abu Yazid; Nazrul Hadi Ismail; Xin Wee Chen; Marymol Koshy; Thuhairah Hasrah Abdul Rahman; Nafeeza Mohd Ismail; Rohana Abdul Ghani

doi:10.1371/journal.pone.0258507

Peer Review History

Original SubmissionJune 28, 2021
29 Jul 2021 Decision Letter - Dorit Samocha-Bonet, Editor PONE-D-21-17598 Safety and Efficacy of Very Low Carbohydrate Diet in Patients with Diabetic Kidney Disease PLOS ONE Dear Dr. Abdul Ghani, 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. The Reviewers asked for more details about the intervention and raised some significant concerns about the statistical methodology. Please address all the comments raised in your response. Please submit your revised manuscript by Sep 12 2021 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. 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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. Please ensure that the registry number for this clinical trial is reported in the main text of the manuscript; 3. In your Methods section, please ensure that sample size calculations are reported, and that main and secondary outcomes are clearly listed, together with the duration of the trial. Also, please describe the location of the study. 4. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match. When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section. Additional Editor Comments (if provided): [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? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: No ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: 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: Zainordin et al provide interesting data on the impact of a VLCKD on diabetic kidney disease, reporting that, compared to a low protein diet, no change in kidney function was observed, but a significant loss in visceral fat together with weight loss and better glucose control were achieved in the study group. General comments: English language needs some revision. Please use people first language throughout the manuscript Keywords: suggest to use the acronym vlckd as vlcbd is not established Abstract Please provide more detail on calorie and macronutrient content of the two diets in the abstract. Introduction: please specify to which nation the national prevalence of t2d refers to. Methods: why such a small age bracket? Patients had a mean BMI compatible with obesity, which is a well established risk factor for CKD and diabetes. Moreover, it is well-known that weight loss improves CKD as the authors report in the discussion. Was the low protein diet in keep with the guidelines for obese diabetic patients with stage 2-3 CKD? Results and discussion Were capillary or urinary ketones tested? If not please mention this in the limitations. Please also mention that only the estimated filtration is available, and no direct kidney function measure was obtained. Was the drop out rate significantly different across groups? If so, please elaborate the finding in the discussion "The main investigators randomized the subjects via block randomization, based on HbA1c and gender to ensure equal numbers within both groups, and subsequent sealed envelopes, to dietary consultations of either very low carbohydrate plus low protein diet (VLCBD) or low protein diet only (LPD). All patients were given the standard dietary and exercise advice which included protein restriction to less than 0.8g/kg/day and low salt diet." It is somewhat unclear throughout the manuscript whether the low carb group also received low protein and low salt advise. Please clarify whether this was the case or not. A low protein diet which is also very low in carbs is necessarily either extremely hypocaloric or very high in fats. Moreover, if fats are not regulated by a diet, they often are saturated. Please provide data on the calorie, protein and fat (quantity as well as quality) consumed at baseline, week 6 and 12, so to understand which is the case. Please elaborate the findings accordingly. Please provide muscle mass change Another study investigating the impact of a very low carbohydrate hypocaloric ketogenic diet on patients with mild kidney failure did not report significant alterations in renal function long term (10.3390/nu12020333). Please complete the introduction/discussion commenting these results. Reviewer #2: My 1st major concern is that the results do not seem correct in Table 2 and 3. For example, the changes in WC seems to be switched between VLCBD and control in Table 3. The within-group differences of medians between baseline and week are 4 and 2 for VLCBD and control respectively. But its shows a reduction of 4 in VLCBD and 2 in control. The similar issue happens to other outcomes in Table 2 and 3 also. Perhaps it is better to present full dataset in supplement table or using dot plots for those primary outcomes. The sample size is too small to compare so many outcomes (more than 20 and 4 tests for each outcome). P value needs to be adjusted for so many tests. The analyses and results in Table 4 are confusing. Details: 1. Remove z values from all tables. 2. Table 1. For categorical variables (e.g. medications), add % also in each group. The numbers for medications do not seem to aligned correctly. If you did not use Wilcoxon signed-rank test for Table 1, remove it from the footnote. 3. Table 2. Some results are questionable: a. Total carbohydrate intake: what are the median within group change? b. Creatinine: control group seems to have an increase of 2 instead of 4. c. Urine microalbumin: the decrease of VLCBD seems to be 25 (50.2-25.5), not -3.2 d. Insulin, UI: the increase in control seems to be 15 not 0. e. LDL: z score of VLCBD should be positive instead of negative 4. Table 3: a. Waist circumference : it seems that the reduction in VLCBD is 2 and the reduction in control is 4. b. Hip: the reduction in control seems to be 4 instead of 0. c. DBP: week 12 used “+-” instead of parentheses. Change misspelled as “hange”. d. Est VAT Mass: the reduction in control seems to be 130 instead of 63. e. Est VAT Vol: the reduction in control seems to be 140. f. Est VAT Area: the reduction in control seems to be more than 27. 5. Table 4 is confusing. a. Since interactions between group and time were included, it is better to show whether the interactions are significant. If the interactions are significant, then need to show simple effects (i.e. group differences at baseline and at week 12 separately). If the interactions are not significant, then you can show main effects. b. Be careful when WC is included in the model for weight. There is obvious collinearity between group and WC change. The significant p value (0.031) is questionable if WC change is included. c. Showing so many different adjustments is confusing to the readers. A model selection is preferred and show the best clinical meaningful/ data fit model as the final model. d. It may be better to adjust for baseline WC and weight in the models. ****** 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 Reviewer #2: 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. 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Revision 1
16 Aug 2021 Author Response We would like to thank both Reviewers for their constructive comments and suggestions. We hereby provide the responses to the questions and comments. Reviewer #1: Zainordin et al provide interesting data on the impact of a VLCKD on diabetic kidney disease, reporting that, compared to a low protein diet, no change in kidney function was observed, but a significant loss in visceral fat together with weight loss and better glucose control were achieved in the study group. General comments: English language needs some revision. Please use people first language throughout the manuscript - Thank you for the comment. The manuscript has been thoroughly revised to correct any typing or grammatical errors and to use people first language throughout the manuscript. Keywords: suggest to use the acronym vlckd as vlcbd is not established - Thank you for the suggestion. However, we would like to maintain the use of VLCBD as oppose to VLCKD, if the reviewer would allow us, as the present study did not confirm ketosis as did Bruci et al. Abstract Please provide more detail on calorie and macronutrient content of the two diets in the abstract. - Thank you for the comment. Details on calorie and macronutrient contents have been included. Introduction: please specify to which nation the national prevalence of t2d refers to. - Thank you for the question. “The prevalence of T2DM in Malaysia has approximately….” has been inserted. Methods: Why such a small age bracket? - Thank you for the question. We had decided to keep the age range small to maintain homogeneity in the study population. Future studies would be looking at slightly more diverse populations in age and levels of eGFR. Patients had a mean BMI compatible with obesity, which is a well-established risk factor for CKD and diabetes. Moreover, it is well-known that weight loss improves CKD as the authors report in the discussion. Was the low protein diet in keep with the guidelines for obese diabetic patients with stage 2-3 CKD? - Thank you for the question. The low protein diet is consistent with the current recommendations from local guidelines for non-dialysis CKD patients as stated in the Introduction section. To the best of our knowledge, none of the current guideline discriminate patients with normal BMI or those with obesity. However, we have added statements to reflect the actual protein intakes in the populations both in the Result and Discussion sections. Results and discussion Were capillary or urinary ketones tested? If not please mention this in the limitations. Please also mention that only the estimated filtration is available, and no direct kidney function measure was obtained. - Thank you for the suggestions. No capillary or urinary ketones were not measure. These have been included in the limitation section. Was the drop out rate significantly different across groups? If so, please elaborate the finding in the discussion. - Thank you for the question. We have added “However, there is no statistically significant drop between the groups.” in the Result section Para 1. "The main investigators randomized the subjects via block randomization, based on HbA1c and gender to ensure equal numbers within both groups, and subsequent sealed envelopes, to dietary consultations of either very low carbohydrate plus low protein diet (VLCBD) or low protein diet only (LPD). All patients were given the standard dietary and exercise advice which included protein restriction to less than 0.8g/kg/day and low salt diet." It is somewhat unclear throughout the manuscript whether the low carb group also received low protein and low salt advise. Please clarify whether this was the case or not. - Thank you for the question and we apologise for the ambiguity. The statement has been modified to – “All patients in both groups were given standard dietary and exercise advice which included protein restriction to less than 0.8g/kg/day and low salt diet.” A low protein diet which is also very low in carbs is necessarily either extremely hypocaloric or very high in fats. Moreover, if fats are not regulated by a diet, they often are saturated. Please provide data on the calorie, protein and fat (quantity as well as quality) consumed at baseline, week 6 and 12, so to understand which is the case. Please elaborate the findings accordingly. - Thank you for the comments. The results of calorie, protein and fat consumption have been included in the Result section Para 2, Pg 12. This has been elaborated on in the Discussion section, Para 2, Pg 20. However, we are unable to provide the data on quality as this was not captured in the data collection. We have included this in the limitation. Please provide muscle mass change. - Thank you for the suggestion. This has been added in Result Para 5, Pg 15. “The VLCBD group demonstrated significant reductions in lean body mass which were not seen in LPD group ( -2113.55 (IQR 1692.83) g vs 476.85 (IQR 2569.85) g, p <0.001).” Another study investigating the impact of a very low carbohydrate hypocaloric ketogenic diet on patients with mild kidney failure did not report significant alterations in renal function long term (10.3390/nu12020333). Please complete the introduction/discussion commenting these results. - Thank you for the suggestion. Bruci et al reported very interesting results. This has been added accordingly in the Introduction section final paragraph and cited as Reference no 14. It has also been included in Discussion section, para 1. References numbering has been adjusted accordingly. Reviewer #2: My 1st major concern is that the results do not seem correct in Table 2 and 3. For example, the changes in WC seems to be switched between VLCBD and control in Table 3. The within-group differences of medians between baseline and week are 4 and 2 for VLCBD and control respectively. But its shows a reduction of 4 in VLCBD and 2 in control. The similar issue happens to other outcomes in Table 2 and 3 also. Perhaps it is better to present full dataset in supplement table or using dot plots for those primary outcomes. The sample size is too small to compare so many outcomes (more than 20 and 4 tests for each outcome). P value needs to be adjusted for so many tests. The analyses and results in Table 4 are confusing. Details: 1. Remove z values from all tables. 2. Table 1. For categorical variables (e.g. medications), add % also in each group. The numbers for medications do not seem to aligned correctly. If you did not use Wilcoxon signed-rank test for Table 1, remove it from the footnote. - Thank you for the suggestions. Amendments have been made accordingly. 3. Table 2. Some results are questionable: a. Total carbohydrate intake: what are the median within group change? - Thank you for the question. The results have been added. b. Creatinine: control group seems to have an increase of 2 instead of 4. c. Urine microalbumin: the decrease of VLCBD seems to be 25 (50.2-25.5), not -3.2 d. Insulin, UI: the increase in control seems to be 15 not 0. - Thank you for the question. However, the data expressed in the tables here were generated by the SPSS statistical analyses software program, with values expressed as median (IQR). Therefore, the data were not simple deductions. The full dataset has been uploaded in a Supplementary File as required. e. LDL: z score of VLCBD should be positive instead of negative - This has been removed as suggested earlier. 4. Table 3: a. Waist circumference : it seems that the reduction in VLCBD is 2 and the reduction in control is 4. b. Hip: the reduction in control seems to be 4 instead of 0. c. DBP: week 12 used “+-” instead of parentheses. Change misspelled as “hange”. d. Est VAT Mass: the reduction in control seems to be 130 instead of 63. e. Est VAT Vol: the reduction in control seems to be 140. f. Est VAT Area: the reduction in control seems to be more than 27. - Thank you for the question. However, the data expressed in the tables here were generated by the SPSS statistical analyses software program, with values expressed as median (IQR). Therefore, the data were not simple deductions. - Lean Muscle Mass changes have been added in the Table - The full dataset has been uploaded in a Supplementary File as required. We apologize for the typing errors and these had been corrected accordingly. 5. Table 4 is confusing. a. Since interactions between group and time were included, it is better to show whether the interactions are significant. If the interactions are significant, then need to show simple effects (i.e. group differences at baseline and at week 12 separately). If the interactions are not significant, then you can show main effects. b. Be careful when WC is included in the model for weight. There is obvious collinearity between group and WC change. The significant p value (0.031) is questionable if WC change is included. c. Showing so many different adjustments is confusing to the readers. A model selection is preferred and show the best clinical meaningful/ data fit model as the final model. d. It may be better to adjust for baseline WC and weight in the models. - Thank you for your comments. The amendments have been done by our co-author accordingly. Some explanations are included in the text as well as the modifications of the table as suggested. Thank you again for your suggestions. We look forward to your positive reviews. Attachments Attachment Submitted filename: Response Letter for Reviewers VLCBD.docx https://doi.org/10.1371/journal.pone.0258507.r002
25 Aug 2021 Decision Letter - Dorit Samocha-Bonet, Editor PONE-D-21-17598R1 Safety and Efficacy of Very Low Carbohydrate Diet in Patients with Diabetic Kidney Disease PLOS ONE Dear Dr. Abdul Ghani, 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. ============================== The reviewers are mostly satisfied with the revised manuscript. Please comment on what seems to be common underreporting of energy intake in the discussion, as per Reviewer 1. If food was not provided to the study participants, please add as a limitation as well as the dietary reporting using 3-days diet diaries. ============================== Please submit your revised manuscript by Oct 09 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://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, Dorit Samocha-Bonet Academic Editor PLOS ONE Journal Requirements: 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 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: All comments have been addressed Reviewer #2: All comments have been addressed ******** 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: Partly Reviewer #2: (No Response) ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: I Don't Know Reviewer #2: (No Response) ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: (No Response) ****** 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: No Reviewer #2: (No Response) ****** 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: The authors have addressed my concerns and the manuscript has improved. However, reported baseline calorie intake is extremely surprising, being very hypocaloric in patients with obesity. I suggest to review records once again and elaborate on this aspect which seems extremely unlikely to be true. Moreover, English language needs extensive revision especially in the newly added parts. Reviewer #2: (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 Reviewer #2: 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.0258507.r003
Revision 2
27 Aug 2021 Author Response Dear Sir, Thank you for your prompt response and further comments and suggestions. I hereby provide the details of the amendments as required. Academic Editor: The reviewers are mostly satisfied with the revised manuscript. Please comment on what seems to be common underreporting of energy intake in the discussion, as per Reviewer 1. If food was not provided to the study participants, please add as a limitation as well as the dietary reporting using 3-days diet diaries. Thank you so much for these suggestions. The points have been included as suggested. Reviewer #1: The authors have addressed my concerns and the manuscript has improved. However, reported baseline calorie intake is extremely surprising, being very hypocaloric in patients with obesity. I suggest to review records once again and elaborate on this aspect which seems extremely unlikely to be true. Thank you for the comments. We have reviewed the records again and confirm the findings. However, we acknowledge the points raised and have included this in the discussion and limitation accordingly. This statement has been added. “With regards to the baseline macronutrients intakes, the notably low baseline calorie consumption could probably be due to considerable under-reporting and under-estimation, both intentionally and unintentionally, as similarly reported by a previous study [25].” References have been adjusted accordingly. Moreover, English language needs extensive revision especially in the newly added parts. We have sent the manuscript for proof reading. The text score was 82%. Corrections have been made accordingly. Thank you again for your suggestions and comments. We look forward to your positive review. Attachments Attachment Submitted filename: Response Letter 2 for Reviewers VLCBD.docx https://doi.org/10.1371/journal.pone.0258507.r004
29 Sep 2021 Decision Letter - Dorit Samocha-Bonet, Editor Safety and Efficacy of Very Low Carbohydrate Diet in Patients with Diabetic Kidney Disease- A Randomized Controlled Trial PONE-D-21-17598R2 Dear Dr. Abdul Ghani, 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, Dorit Samocha-Bonet Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0258507.r005
Formally Accepted
4 Oct 2021 Acceptance Letter - Dorit Samocha-Bonet, Editor PONE-D-21-17598R2 Safety and Efficacy of Very Low Carbohydrate Diet in Patients with Diabetic Kidney Disease- A Randomized Controlled Trial Dear Dr. Abdul Ghani: 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. Dorit Samocha-Bonet Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0258507.r006

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