Dear Dr. Bakker,

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 Dec 07 2025 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'.
• 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: https://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,

Hidetaka Hamasaki

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. 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.

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?

Reviewer #1: Partly

Reviewer #2: Partly

**********

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

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: This manuscript by Schoonhoven et al., titled “Glucose dysregulation in hospitalized non-critically ill patients with a severe infection: a prospective study using continuous glucose monitoring” investigated the prevalence and course of dysglycaemia in non-critically ill adults hospitalized for severe infection using CGM, the authors find that in 90 patients, dysglycaemia is common in both diabetic and non-diabetic inpatients with infection and CGM could improve detection and management. The study provides interesting pilot data but the small sample size and low number of clinical events limit the robustness of conclusions, particularly regarding associations between dysglycaemia and outcomes. Larger multicenter studies are needed to confirm these findings. Additionally, several methodological and interpretative issues need to be addressed.

In the method section of study design, Inclusion and exclusion criteria are clear, but justification for excluding corticosteroid users should be elaborated, does this exclusion bias the sample toward less severe infections? Please clarify whether “severe infection” per inclusion criteria.

In Statistical Analysis, it is stated that p<0.05 was considered significant, but multiple comparisons were made without correction. Please comment on whether a correction (e.g., Bonferroni or FDR) was considered. Was any regression modeling performed to adjust for potential confounders such as age, BMI, or diabetes status when exploring associations with dysglycaemia?

In the discussion, the authors conclude that CGM may “allow earlier intervention” but as the study was blinded and observational, this inference is speculative. Please temper this statement or support it with cited intervention studies.

The reported 55% rate of hypoglycaemia (including in non-diabetic patients) seems high. Could sensor compression or first-day calibration bias explain part of this? Consider adding a sensitivity analysis excluding the first 24 hours of CGM data.

Reviewer #2: The topic is clinically relevant and timely, as glucose instability in acute infection is common but under-characterized outside the ICU setting. The prospective design and adherence to STROBE standards are strengths. However, the study as presented remains primarily descriptive and exploratory. The analyses are insufficiently detailed, the comparisons lack statistical rigor, and several methodological and interpretive limitations reduce the strength of the conclusions. Substantial revision is required before this manuscript can be considered for publication.

1. The study relies mainly on descriptive and univariate comparisons between patients with and without diabetes. To enhance interpretability, apply multivariate regression (logistic or linear, as appropriate) to evaluate associations between dysglycaemia metrics (such as mean glucose, time in range) and outcomes (ICU admission, mortality, hospital stay). Also consider adjusting for potential confounders such as age, BMI, CRP, and infection severity.

2. Report effect sizes and 95% confidence intervals, not only p-values.

3. The study concludes that dysglycaemia was common but not associated with clinical outcomes. Given the small number of adverse events, this result may be due to limited power rather than a true absence of association. The authors should clearly state the low event rate as a limitation.

4. Discuss whether dysglycaemia might serve as an early biomarker for clinical deterioration, rather than an independent outcome predictor.

5. The analysis would be more informative if additional variables were included such as type and site of infection, nutritional intake, IV glucose, and insulin dosing during admission (noting that severity scores like SIRS/qSOFA are already reported at baseline). Without these, the ability to interpret the mechanisms or contributors to dysglycaemia is limited.

6. Expand discussion on why hypoglycaemia and hyperglycaemia patterns differ between groups.

7. Provide a mechanistic rationale connecting infection-related stress responses with CGM-detected glycaemic patterns.

8. Change the conclusion that CGM “may improve outcomes,” which is not supported by the presented data.

9. Define “severe infection” operationally—were diagnoses microbiologically confirmed or purely clinical?

10. Clarify whether HbA1c data were unavailable or simply not collected; this affects interpretation of undiagnosed diabetes.

**********

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.]

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.

Glucose dysregulation in hospitalized non-critically ill patients with a suspected infection: a prospective study using continuous glucose monitoring

PONE-D-25-49860R1

Dear Dr. Bakker,

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,

Hidetaka Hamasaki

Academic Editor

PLOS One

Additional Editor Comments (optional):

Thank you for submitting the revised manuscript.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #1: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions??>

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

Reviewer #1: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

**********

Reviewer #1: (No Response)

**********

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

**********