PONE-D-24-25485Effects of insulin resistance and β-cell function on diabetic complications in Korean diabetic patientsPLOS ONE

Dear Dr. Lee,

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PLOS ONE

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Reviewers' comments:

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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: Yes

Reviewer #3: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

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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

Reviewer #3: No

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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

Reviewer #3: Yes

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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: In the manuscript titled "Effects of insulin resistance and β-cell function on diabetic complications in Korean diabetic patients," the authors explore how insulin resistance and β-cell function relate to diabetic complications in Korean patients. This research question is compelling, and the findings are well-supported, offering potential clinical significance. With some adjustments for clarity and detail, this work should be ready for publication.

•

The abstract could be improved by including more specifics about the clinical implications of the findings.

•

The introduction does a good job of outlining the complex nature of diabetes. However, it could be clearer about the specific gaps in the current research that this study addresses, especially regarding Korean diabetic patients. It would help to emphasize why it's important to study this particular group.

•

The methods section is detailed, explaining the use of a common data model (CDM) and defining how insulin resistance and β-cell function were measured. It would be useful to include more details about how patients were selected and the specific statistical methods used to calculate hazard ratios. Addressing potential biases and how they were mitigated would strengthen this section. It’s also important to explain how patient data was anonymized and how any missing data was managed.

• For clarity, some sentences could be simplified. For instance, instead of "While approximately 75–85% of diabetic individuals fit the traditional criteria for type 2 diabetes...," you could say, "Approximately 75–85% of diabetic patients meet the traditional criteria for type 2 diabetes, but many show characteristics of both insulin resistance and β-cell dysfunction."

•

The discussion should compare the findings with previous studies, particularly those involving other ethnic groups, to highlight the unique aspects of the results. The conclusion could more clearly outline the practical implications, such as how these findings might influence screening or treatment decisions based on insulin resistance and β-cell function. Discussing potential reasons behind the associations found, such as cultural or genetic factors specific to Korean populations, would add depth.

Reviewer #2: Authors looked into the dose-response relationship of beta-cell function and diabetes complications in diabetic individuals.

Abstract is poor. Patient characteristics must be stated in the results section not method. A brief explanation of your data source will be useful in the methods. Also confidence intervals for adjusted hazard ratios must be reported.

Second paragraph of the introduction was too long. I think you can summarize it and talk less about the swedish diabetes classification and more about the importance of beta-cell function and diabetes complications.

Paragraph 3 in introduction: Aim of study is not clear. Why, despite the other similar papers in different countries, it is important to investigate the relationship in Korean population?

Your follow-up duration is vague. You did not report it anywhere as I check. Please calculate it. Moreover, I also suggest subgroup analysis on those with a follow-up duration <2 years (Short-term outcome).

Did you include all the variables in your regression model for adjustment? Or just the statistically significant variables. I suggest to perform three regression models to have a better comparison: model 1= unadjusted, model 2= age and sex adjusted, model 3= adjusted with all confounding variables.

Baseline characteristics of the patients must be stated using numbers (at least for important variables such as age, sex,

Results were poorly organized. I think separation into sections based on different diabetic complications such as retinopathy, nephropathy, and CVD, and then report each relevant finding in its specific section might be suitable.

Again all the confidence intervals are missed. Please report. Also provide p-values and statistical tests for tables 1&2.

Discussion is well-written. However, adding a paragraph about the possible molecular mechanisms underneath the association of diabetic retinopathy or CVD risk with beta-cell function and insulin resistance.

Reviewer #3: Review Comment:

1- The study investigates the associations between insulin resistance (IR), β-cell function, and diabetic complications using a cohort from a common data model (CDM) database. While the topic is relevant, the study's novelty is not well articulated in the abstract, which raises concerns about its contribution to the existing body of knowledge.

2- Methodology: The study employs appropriate methodologies, including the calculation of HOMA-IR and HOMA-β, and robust statistical analyses using Cox proportional hazards models. The inclusion of anthropometric measurements, laboratory tests, and detailed statistical adjustments for variables such as age, gender, BMI, and medication use strengthens the study’s methodology. However, the lack of demographic details such as age, gender, and race are significant omissions that hinder the assessment of the study’s generalizability. The exclusion criteria, particularly the exclusion of subjects with incomplete data or prior complications, need more justification to ensure that the study's findings are not biased. Additionally, the stratification of patients based on quartiles of HOMA-IR and HOMA-β is appropriate, but the rationale behind these specific stratifications and reference categories should be clarified.

3- Ethical Considerations: The authors mention that the study received approval from the hosting institute and used anonymized data, which addresses privacy concerns. However, the absence of informed consent is a critical issue. The abstract does not clearly state whether this research qualifies as a split study, where data originally collected for a different purpose are repurposed. It’s important that the authors clarify this point and detail how ethical approval covered the secondary use of such data.

4- References: The study cites only 15 references, which seems relatively few given the complexity of the topic. This limited reference list may indicate that the study has not fully engaged with the breadth of existing literature, particularly in a field as well-studied as diabetes and its complications. A more comprehensive review of relevant studies would strengthen the contextualization and credibility of the findings.

5- Conclusion: While the study potentially offers valuable insights, several aspects need further clarification and expansion. The abstract should clearly articulate the novelty of the research, include demographic information, address ethical concerns related to the possible use of previously collected data, and consider expanding the reference list to demonstrate a thorough engagement with the existing literature. These major revisions would significantly enhance the rigor and transparency of the study.

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Reviewer #1: Yes: Solaleh Emamgholipour

Reviewer #2: No

Reviewer #3: No

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Effects of insulin resistance and β-cell function on diabetic complications in Korean diabetic patients

PONE-D-24-25485R1

Dear Dr. Lee,

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.

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Kind regards,

Mohammad Reza Mahmoodi, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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

Reviewer #3: All comments have been addressed

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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

Reviewer #2: Yes

Reviewer #3: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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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: Yes

Reviewer #3: Yes

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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

Reviewer #2: Yes

Reviewer #3: Yes

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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 thoroughly addressed the reviewers' comments, improving the study's methods, clarity, and strength. The manuscript is now well-organized with better discussion and interpretation, making it more suitable for publication.

Reviewer #2: Thanks for your precise and reasonable responses. I have no comments to add. I recommend the acceptance.

Reviewer #3: (No Response)

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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: Yes: Solaleh Emamgholipour

Reviewer #2: No

Reviewer #3: No

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