PONE-D-24-58961HYPERVITAMINOSIS A IN TYPE 2 DIABETES AND ITS RELAZION WITH RENAL FUNCTION AND CARDIOVASCULAR COMPLICATIONS.PLOS ONE

Dear Dr. Zoppini,

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ACADEMIC EDITOR: Kindly revise and resubmit as per the reviewer's comments

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Academic Editor

PLOS ONE

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Additional Editor Comments:

Based on the reviewer's comment kindly revise and resubmit.

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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: Partly

Reviewer #2: Partly

Reviewer #3: Partly

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

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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: No

Reviewer #2: Yes

Reviewer #3: No

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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: Abstract

Under “Research Design and Method”, please provide statements on the specific study site, including the name of the study site and the sampling technique adopted for this study.

Under “Results” provide figures to support the statement “The HVA prevalence was significantly higher in patients with cardiovascular complications (CVD). Nevertheless, when patients with CVD were stratified according to renal function, the latter emerged as the main factor associated with HVA”. For example what is the proportion and the p-value? These are necessary to appreciate the outcome of this study.

Under “Conclusions”, the statement “The main alteration of vitamin A in ambulatory patients affected by type 2 diabetes is hypervitaminosis” should be rephrased for clarity.

Main Text

Introduction

The last statement should be moved to the methodology subsection. It is most appropriate to be included in the statements of inclusion and exclusion criteria.

Under “Research Design and Method”, by describing the study site as “our diabetic clinic” does not help international readership. Please state the exact name for the study site.

State the specific duration for the overnight fast.

What constitutes "other biochemical measurements"?

The statement on height and weight measurement should come before body mass index calculation.

Before Statistical Analysis subsection, the authors should provide statements on the sample size determination.

Concerning these statements under “Results”, Vitamin A was determined in 200 ambulatory patients affected by type 2 diabetes. Patients who took vitamin supplements within the six months before the study were excluded. The cut-off levels of vitamin A were ≤ 1.04 and > 2.79 μmol/L for either hypovitaminosis or hypervitaminosis, respectively. These statements cannot be the narratives for the result outcomes. They are better suited for the subsection on methodology.

The authors found that “The sex distribution of HVA was substantially the same, 22.4% women and 32.2% men with a p value of 0.144.” What sampling technique did the authors adopt in arriving at this outcome for the sex distribution?

The authors also suggested that “the levels of VA increased throughout the categories of CKD; G1= 2.26±0.48; G2= 2.40±0.68; G3a= 2.72±0.71; G3b 2.56±0.61 and G4 (only 3 subjects) 3.45±0.79, p for trend <0.001. The increasing level of vitamin A was significant starting from the CKD3a category (post hoc test of Scheffè). These statements of result claimed by the authors in Figure 2 do not exist in the said Figure 2. So it was difficult to verify the outcome.

In the narrative for Table 2, the authors should report the odd ratio, confidence interval and p-values for the association between obesity and HVA.

The subsection “Conclusions” should be rendered “Discussions”

Under “Conclusions”, The statement “Notably, vitamin A concentration began to increase from stage CKD G3a is not supported by the said "Figure 2 ". Please clarify.

Reviewer #2: I appreciate the opportunity to review this manuscript and contribute to the scholarly process. The study addresses an important yet underexplored aspect of metabolic health, and I look forward to providing constructive feedback.

General Comments:

1. Please add line numbers to facilitate clear and precise communication during the review process.

2. Include a title for the Background or Introduction section after the abstract for better organization.

3. Consider structuring the final section as Discussion and Conclusion rather than just Conclusion to ensure a comprehensive synthesis of findings.

Specific comments

1. The term "RELAZION" in the title is unclear. Could you clarify its intended meaning? If you meant "relation" or "relationship," I recommend revising the title for clarity and accuracy.

2. What are the implications of hypervitaminosis A on diabetes treatment?

3. Does it pose a real concern for diabetes outcomes, or could it potentially influence treatment efficacy?

4. Are there any established guidelines recognizing hypervitaminosis A as a complication, a factor influencing disease progression, or a determinant of treatment outcomes?

5. How does this study contribute to the existing body of knowledge, and what is its practical significance for clinicians managing diabetes?

6. Are you suggesting that hypervitaminosis A could serve as an indicator of early-stage chronic kidney disease (CKD) in diabetic patients?

7. If so, what are the potential mechanisms by which hypervitaminosis A could contribute to or reflect kidney dysfunction in this context?

8. What are the clinical implications of these findings for early diagnosis and management of CKD in diabetic individuals?

Reviewer #3: Title language should be in english - relation and not relazion

Introduction -

Heading is missing

Vitamin A shoild not be abbreviated

Retinoic and not retinoid acid

Introduction doesnt emphasize the role of Vitamin A in Type 2 diabetes. Direct implication of Vit A in type 2 diabetes was nto mentioned.

Research design and method

Inclusion criteria reason out the age range and sex. Was there any grouping done based on age or sex. If not why wasit not done. Did the patients used insulin supplement? Were they included or excluded. Does exclusion criteria inludes any terminal or old age related illness. What were the biochemical blood measurements done. Not reported in the study. Only creatine was done. Renal function test was not carried out. Severity scale was not mentioned in the research design. Grouping based on severity of the diseases was not done.The sentences should not use the word WE or I. Past tense should be used. is to be corrected to was.

"The main clinical and anthropometric characteristics" - where are the anthrometric characteristics

Correlation between Cardiovascular disease (CVD) and Vit A was not done. What are evaluations done withrespect cardiovascular.

Conclusion

Tense correction in sentences. Should be in one tense. "We" should not be used.

Comparison with other studies which were carried out between Vita A and CVD or Vit A and Renal should be added. Revieing past literature with present study should be carried out. The conclusion doesnt provide information on statistical significane or correlation.

Review. Significant defiency in the study design and methodology doesnt substanstiate the role of Vit A in CVD and Renal function.

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Reviewer #1: Yes:  Dr. Sylvester Yao Lokpo

Reviewer #2: No

Reviewer #3: No

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Submitted filename: Review Comments for PLOS One.docx

HYPERVITAMINOSIS A IN TYPE 2 DIABETES AND ITS RELAZION WITH RENAL FUNCTION AND CARDIOVASCULAR COMPLICATIONS.

PONE-D-24-58961R1

Dear Dr. Zoppini,

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.

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Kind regards,

Tarek Samy Abdelaziz, MD,FRCP

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewer #2:

Reviewer #3:

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 #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 #2: No

Reviewer #3: Yes

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

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 #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 #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 #2: I truly appreciate your response. As a suggestion for future related studies, I strongly believe it is essential to clearly define the significance of the research by identifying specific gaps in the existing literature. Without a well-articulated rationale and clearly stated implications, particularly for patients with type 2 diabetes, such studies may lack direction and could result in a misallocation of valuable resources.

Reviewer #3: The author addressed all queries from the past review..The author had provuded information wherever asked for.

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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 #2: No

Reviewer #3: No

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