Dear Dr. Stenberg,

Thank you very much for submitting your manuscript "The impact of duration of diabetes on remission rates after bariatric surgery" (PMEDICINE-D-19-02752) for consideration at PLOS Medicine.

Your paper was evaluated by a senior editor and discussed among all the editors here. It was also discussed with an academic editor with relevant expertise, and sent to independent reviewers, including a statistical reviewer. The reviews are appended at the bottom of this email and any accompanying reviewer attachments can be seen via the link below:

[LINK]

In light of these reviews, I am afraid that we will not be able to accept the manuscript for publication in the journal in its current form, but we would like to consider a revised version that addresses the reviewers' and editors' comments. Obviously we cannot make any decision about publication until we have seen the revised manuscript and your response, and we plan to seek re-review by one or more of the reviewers.

In revising the manuscript for further consideration, your revisions should address the specific points made by each reviewer and the editors. Please also check the guidelines for revised papers at http://journals.plos.org/plosmedicine/s/revising-your-manuscript for any that apply to your paper. In your rebuttal letter you should indicate your response to the reviewers' and editors' comments, the changes you have made in the manuscript, and include either an excerpt of the revised text or the location (eg: page and line number) where each change can be found. Please submit a clean version of the paper as the main article file; a version with changes marked should be uploaded as a marked up manuscript.

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We expect to receive your revised manuscript by Oct 01 2019 11:59PM. Please email us (plosmedicine@plos.org) if you have any questions or concerns.

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We look forward to receiving your revised manuscript.

Sincerely,

Adya Misra,

Senior Editor

PLOS Medicine

plosmedicine.org

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Requests from the editors:

Title, please recast to include a study descriptor. Perhaps:

Association with bariatric surgery and the duration of type 2 diabetes in Sweden 2007-2015: a retrospective cohort study

Abstract – this is structured with 3 sections: Background, Methods and Findings and Conclusions and please ensure the final sentence of the Methods and Findings section includes a sentence on the limitations of the study.

Abstract – please include cities and some summary participant information such as age, sex, BMI, etc

Data – an author cannot be a point of contact – please find another contact point.

At this stage, we ask that you include a short, non-technical Author Summary of your research to make findings accessible to a wide audience that includes both scientists and non-scientists. The Author Summary should immediately follow the Abstract in your revised manuscript. This text is subject to editorial change and should be distinct from the scientific abstract. Please see our author guidelines for more information: https://journals.plos.org/plosmedicine/s/revising-your-manuscript#loc-author-summary

References in the main text – please use square brackets and remove superscript

Was written consent provided by participants?

Did your study have a prospective protocol or analysis plan? Please state this (either way) early in the Methods section.

a) If a prospective analysis plan (from your funding proposal, IRB or other ethics committee submission, study protocol, or other planning document written before analyzing the data) was used in designing the study, please include the relevant prospectively written document with your revised manuscript as a Supporting Information file to be published alongside your study, and cite it in the Methods section. A legend for this file should be included at the end of your manuscript.

b) If no such document exists, please make sure that the Methods section transparently describes when analyses were planned, and when/why any data-driven changes to analyses took place.

c) In either case, changes in the analysis—including those made in response to peer review comments—should be identified as such in the Methods section of the paper, with rationale.

Please provide a STROBE reporting guidelines (submitted as a Supp file and ensure paragraph and sections are used instead of page numbers – these will change in the event of publication.)

Comments from the reviewers:

Reviewer #1: I have read with great interest the paper by Jans et al. They have used the large Swedish registry data on bariatric surgeries, to answer the question that which factors contribute to remission of T2DM after surgically-induced weight loss. The study was well-designed and -written. I have only some very minor comments to it.

Abstract

At first read, it was slightly difficult to capture the concept of correlation in the sentence: "The chance of achieving complete remission correlated…" since there were both continuous (duration of diabetes, age, Hba1c) and dichotomous variables (insulin treatment) in the analyses. Can this be opened, e.g. by adding units after each OR.

Introduction

Obesity rates are low. Any data available for larger prevalences, which is the case in most countries?

Methods

Nro of patients in each operation type could belong to the methods, however if the authors wish, it can as well remain in the results section as it is now.

Results

A flow chart of the available patients would be useful. The percentages are hard to follow. For example in the sentence "5388 patients were available for analyses on pharmaceutical use at 5 years (98%)": What does the 98% represent?

Reviewer #2: Thanks for the chance to review this manuscript. This study verified that longer T2DM duration, insulin therapy prior to surgery, lower BMI were negative predictors to predict T2DM remission after RYGB/SG with a large sample size and longer follow-up period. Although these data from several registry systems was high-quality, some valuable clinical variables were missing, for instance, fasting C peptide.

Many previous studies have found T2DM duration, C peptide, age, BMI and insulin usage were powerful predictive factors, and thus the novelty of this study is limited. Additionally, during follow-up period, most patients were lost, which affected the credibility of the conclusions.

Reviewer #3: Due to the imbalanced effects of bariatric surgery on clinically improving metabolic disorders among patients, exploring the factors that affect surgery-induced benefits is quite necessary. In this study, the author provides convincing evidences with large sample size to support his conclusion that the remission of T2DM induced by bariatric surgery is negatively correlated to duration of diabetes and increases in patient with recent onset diabetes and those without insulin treatment. These findings are meaningful for clinician to make decision on treating T2DM by surgery, a treatment that, although effective, cause irreversible changes in patient's GI track.

However, as the author mentioned in the manuscript, the retrospective property of this study limits its significance, other variables among subjects such as distinct behaviors during as long as 5 years may also contribute to the uneven diabetic remission rate after surgery, which need to be further and deeply explored. Whereas the high-quality data and large sample size of this study still make it convincible, and it should be eligible to be published in Plos medicine.

Reviewer #4: I confine my remarks to statistical aspects of this paper. In general, these were fine, although I do wonder why the authors did not do a Cox proportional hazards survival analysis.

Some comments/suggestions:

Line 127-8 I think it would be better to use "proportion of excess weight". I am guessing that the people in the study varied a lot in how overweight they were. If a person is 100 kg overweight and another is 200 kg overweight and each loses 100 kg, it does not have the same effect. Maybe there is no good estimate of ideal weight, but even BMI (flawed though that is) could be used.

Table 1 - What about exactly 10 years of education? or exactly3 years of higher education?

Figures - stacked histograms are not a good method (see the work of William S. Cleveland). Line charts would be better with duration on the x axis, percent on the y axis and a line for each outcome.

Peter Flom

Any attachments provided with reviews can be seen via the following link:

[LINK]

Dear Dr. Stenberg,

Thank you very much for re-submitting your manuscript "Association with duration of type 2 diabetes and remission rates after bariatric surgery in Sweden 2007-2015: a registry-based cohort study" (PMEDICINE-D-19-02752R1) for review by PLOS Medicine.

I have discussed the paper with my colleagues and the academic editor. I am pleased to say that provided the remaining editorial and production issues are dealt with we are planning to accept the paper for publication in the journal.

The remaining issues that need to be addressed are listed at the end of this email. Any accompanying reviewer attachments can be seen via the link below. Please take these into account before resubmitting your manuscript:

[LINK]

Our publications team (plosmedicine@plos.org) will be in touch shortly about the production requirements for your paper, and the link and deadline for resubmission. DO NOT RESUBMIT BEFORE YOU'VE RECEIVED THE PRODUCTION REQUIREMENTS.

***Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.***

In revising the manuscript for further consideration here, please ensure you address the specific points made by each reviewer and the editors. In your rebuttal letter you should indicate your response to the reviewers' and editors' comments and the changes you have made in the manuscript. Please submit a clean version of the paper as the main article file. A version with changes marked must also be uploaded as a marked up manuscript file.

Please also check the guidelines for revised papers at http://journals.plos.org/plosmedicine/s/revising-your-manuscript for any that apply to your paper. If you haven't already, we ask that you provide a short, non-technical Author Summary of your research to make findings accessible to a wide audience that includes both scientists and non-scientists. The Author Summary should immediately follow the Abstract in your revised manuscript. This text is subject to editorial change and should be distinct from the scientific abstract.

We expect to receive your revised manuscript within 1 week. Please email us (plosmedicine@plos.org) if you have any questions or concerns.

We ask every co-author listed on the manuscript to fill in a contributing author statement. If any of the co-authors have not filled in the statement, we will remind them to do so when the paper is revised. If all statements are not completed in a timely fashion this could hold up the re-review process. Should there be a problem getting one of your co-authors to fill in a statement we will be in contact. YOU MUST NOT ADD OR REMOVE AUTHORS UNLESS YOU HAVE ALERTED THE EDITOR HANDLING THE MANUSCRIPT TO THE CHANGE AND THEY SPECIFICALLY HAVE AGREED TO IT.

Please ensure that the paper adheres to the PLOS Data Availability Policy (see http://journals.plos.org/plosmedicine/s/data-availability), which requires that all data underlying the study's findings be provided in a repository or as Supporting Information. For data residing with a third party, authors are required to provide instructions with contact information for obtaining the data. PLOS journals do not allow statements supported by "data not shown" or "unpublished results." For such statements, authors must provide supporting data or cite public sources that include it.

If you have any questions in the meantime, please contact me or the journal staff on plosmedicine@plos.org.

We look forward to receiving the revised manuscript by Oct 30 2019 11:59PM.

Sincerely,

Adya Misra, PhD

Senior Editor

PLOS Medicine

plosmedicine.org

------------------------------------------------------------

Requests from Editors:

Please remove "association with" from the start of the title

Abstract “other important factors” – please be specific in text. In this case, specify or remove;

Author summary – please remove ‘obesity surgery’ as I don’t think this is an official term, is it?

- There are some "p<0.0001" in the abstract and results – please alter to <0.001, per house style

Line 221 – “4192 patients received oral treatment” please be specific, of what? And again line 226, please also correct anywhere else in the main text.

- "In this study, we found that ... was ..." at line 58, or similar (and around line 88)

- I'd go for "negatively [or "inversely"] associated" rather than "negatively correlated"

- square brackets needed for refs in the main text

Comments from Reviewers:

Any attachments provided with reviews can be seen via the following link:

[LINK]

Dear Dr. Stenberg,

On behalf of my colleagues and the academic editor, Dr. Kirsi H. Pietiläine, I am delighted to inform you that your manuscript entitled "Duration of type 2 diabetes and remission rates after bariatric surgery in Sweden 2007-2015: a registry-based cohort study" (PMEDICINE-D-19-02752R2) has been accepted for publication in PLOS Medicine.

PRODUCTION PROCESS

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PROFILE INFORMATION

Now that your manuscript has been accepted, please log into EM and update your profile. Go to https://www.editorialmanager.com/pmedicine, log in, and click on the "Update My Information" link at the top of the page. Please update your user information to ensure an efficient production and billing process.

Thank you again for submitting the manuscript to PLOS Medicine. We look forward to publishing it.

Best wishes,

Adya Misra, PhD

Senior Editor

PLOS Medicine

plosmedicine.org