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Exploring the Associations of Neck Circumference, Blood Pressure, CRP, and Insulin Resistance on the Visceral Adiposity Index: Insights from a Cross-Sectional Study

Endocrines 2024, 5(4), 538-546; https://doi.org/10.3390/endocrines5040039
by Lucas Fornari Laurindo 1,2,*, Francine Cruz Camargo 3, Alessandra Perfeito 3, Bruno Benedito Ciano 3, Clara Tainá Coelho 3, Gleice Assis Apolinário 3, Isabela do Nascimento Vicentin 3, Jéssica Cambui Andreasi 3, Beatriz Leme Boaro 1, Ricardo José Tofano 2,4, Cláudia Rucco Penteado Detregiachi 3,4, Jesselina Francisco dos Santos Haber 2, Sandra Maria Barbalho 2,4,5,*, Lance Alan Sloan 6,7, Kátia Portero Sloan 6, Antonelly Cassio Alves de Carvalho 4, Marie Oshiiwa 5, Patrícia Cincotto dos Santos Bueno 2, Tereza Laís Menegucci Zutim 2, Rebeca Maria Siqueira da Silva 1, Eduardo Federighi Baisi Chagas 2,4, Marcelo Dib Bechara 2,4 and Karina R. Quesada 2,3,4,5add Show full author list remove Hide full author list
Reviewer 1: Anonymous
Reviewer 2: Anonymous
Reviewer 3: Anonymous
Endocrines 2024, 5(4), 538-546; https://doi.org/10.3390/endocrines5040039
Submission received: 6 May 2024 / Revised: 7 November 2024 / Accepted: 18 November 2024 / Published: 20 November 2024
(This article belongs to the Special Issue Advances in Diabetes Care)

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

 

The author performed a cross-sectional study aimed to investigate the relationship between Visceral Adiposity Index (VAI) and anthropometric, biochemical, and insulin resistance (IR) parameters, in 88 men and 72 women (of clearly different age) at risk of CVD (not clear the meaning).

They found, as expected, that VAI revealed noteworthy and positive correlations with all anthropometric parameters assessed (p<0.0001). Furthermore, significant positive associations were noted between VAI and total cholesterol in women (p=0.0064), glycemia in men (p=0.0105), and LDL-c (p<0.01) and triglycerides in both genders (p˂0.0001). A significant negative association was observed between VAI and HDL-c in both genders (p<0.0001). Notably, the correlation between VAI and total cholesterol in men, glycemia in women, and CRP in both genders was not found to be significant. However, a significant relationship between VAI and IR parameters was observed in both sexes (p<0.05). The results obtained from our study suggest that VAI functions as a simple and non-intrusive instrument, demonstrating significant effectiveness in identifying metabolic changes primarily associated with adipose tissue dysfunction, particularly dyslipidemia.

Major criticisms

The issue has already been the object of several studies; the authors should consider literature previous to 2014 (Nutr Metab Cardiovasc Dis. 2009 Mar;19(3):198-204- Obes Surg. 2009 Jun;19(6):745-50), where similar results have been reported in greater casistics. There are also several reviews on the same topic.

 

Comments on the Quality of English Language

no comments

Author Response

Dear Reviewer,

Thank you for your thoughtful review of our manuscript titled "Exploring the Influence of Neck Circumference, Blood Pressure, CRP, and Insulin Resistance on the Visceral Adiposity Index: Insights from a Cross-Sectional Study." We appreciate your constructive feedback and suggestions.

We have carefully considered your comments and have made significant revisions to strengthen our manuscript. Specifically, we have included a new analysis that examines the impact of neck circumference (NC), blood pressure (BP), C-reactive protein (CRP), and insulin resistance on the Visceral Adiposity Index (VAI) across a more diverse outpatient cardiology population. This analysis not only reinforces our findings regarding sex-specific variations in VAI but also highlights the importance of these anthropometric and metabolic markers in cardiovascular risk assessment.

Furthermore, we emphasize that while similar results may exist in the literature, our study provides unique insights into the specific Brazilian population under investigation. Our findings underscore the variability and complexity of these relationships, demonstrating the relevance of NC and BP as indicators of visceral adiposity across different VAI quartiles. Importantly, our multiple linear regression analysis revealed that these factors collectively explain only a small proportion of VAI variance, suggesting the need for further exploration in clinical settings.

We have marked all the corrections and additions in yellow throughout the manuscript for your convenience. We kindly invite you to review these changes, which we believe have substantially enhanced the scientific rigor and impact of our study.

Highlighted by our study, the diverse cardiometabolic profiles of the individuals attending a cardiology outpatient clinic underscore significant findings: from notable sex-specific disparities in anthropometric and metabolic markers to robust correlations between Visceral Adiposity Index (VAI) and insulin resistance parameters among men. Notably, analyses by VAI quartiles revealed distinct associations, including elevated systolic blood pressure and larger neck circumference in higher quartiles, emphasizing pivotal cardiovascular risk factors linked with visceral adiposity.

  • Now, the study sample consists of 152 men and 116 women from a cardiology outpatient clinic, with men having a mean age of 55.4 years, mean BMI of 29.7 kg/m², and waist circumference of 101.6 cm. Women showed comparable distributions but differed significantly in neck circumference, total cholesterol, and LDL cholesterol levels.

  • Significant correlations were found between VAI and insulin resistance parameters among men, with insulin (ρ=-0.218, p=0.006) and HOMA-IR (ρ=-0.213, p=0.008) showing negative correlations, indicating stronger associations with these parameters in the total sample.

  • Analysis by VAI quartiles demonstrated distinct associations, with individuals in higher quartiles exhibiting elevated systolic blood pressure (p=0.023) and larger neck circumference (p<0.001), highlighting potential cardiovascular risk factors associated with visceral adiposity.

  • Multiple linear regression analyses adjusted for sex and age revealed that neck circumference, blood pressure, C-reactive protein, cholesterol levels, HbA1C, fasting glucose, insulin, and HOMA-IR did not significantly predict VAI values, indicating that these variables collectively explain only a small proportion of VAI variance (R2 ranging from 0.001 to 0.011).

We believe that these additions substantially enhance the scientific rigor and impact of our manuscript. Therefore, we kindly request reconsideration for publication, highlighting the novel contributions of our study to the field of cardiometabolic health and emphasizing the population-specific nature of these indicators.

Thank you once again for your valuable feedback and consideration.

Reviewer 2 Report

Comments and Suggestions for Authors

This is and explorative and pilot study for Brazilians to verify the ability of a new personalized index, Visceral Adiposity index, to be used as a predictive tool for cardiovascular risk. 

Although the overall investigated population is relatively poor for this kind of study, it must be highlighted that men are much older than women.

Moreover the race of patients are not declared and this might affect the significance of results. Also to explore the fertility age, compared with the menopausal age, would have been critical for the interpretation of findings in women.

Pearson analysis were not adjusted for counfoundig factors such as concomitant diseases or therapies and age, both for men and women. Again to explore the impact of the menopausal state in women

Also a marker of CV risk might improve the significance of the study to explore the predictive significance of VAI.

Discussion is too much speculative and funded on studies performed by other authors, giving to many details of their researches, and reducing, then, originality of the presented study.

Comments on the Quality of English Language

the engllish language should be improved in a more narrative way

Author Response

Thank you sincerely for dedicating your time and expertise to reviewing our manuscript. Your insightful comments and suggestions have been invaluable in refining our study on the predictive potential of the Visceral Adiposity Index (VAI) for cardiovascular risk among Brazilians. Please, find the modifications highlighted in yellow throughout the manuscript.

Reviewer Comment 1: "This is an explorative and pilot study for Brazilians to verify the ability of a new personalized index, Visceral Adiposity Index, to be used as a predictive tool for cardiovascular risk."

Response: Indeed, our study aims to pioneer the application of the Visceral Adiposity Index (VAI) in predicting cardiovascular risk among Brazilians, addressing a critical gap in personalized medicine. We have provided robust sex-specific data from a diverse cardiology outpatient clinic cohort, which adds valuable insights into cardiometabolic health markers.

Regarding the speculative nature of our discussion, we have carefully revised and refocused our interpretations to underscore the original contributions of our study findings. By minimizing reliance on external studies and emphasizing our own data, we aim to amplify the novelty and impact of our manuscript.

Now, our discussion focuses on specific findings from our study. Our study sample, comprising 152 men and 116 women attending a cardiology outpatient clinic, exhibited diverse characteristics related to cardiometabolic health. Among men, notable findings included a mean age of 55.4 years (SD=14.4), mean BMI of 29.7 kg/m² (SD=5.4), and waist circumference of 101.6 cm (SD=16.0). Significant differences were observed in neck circumference, total cholesterol, and LDL cholesterol levels between sexes, underscoring sex-specific variations in cardiometabolic profiles (Table 1).

Table 1 compares the mean and standard deviation of study variables between men and women, highlighting significant differences in neck circumference, total cholesterol, and LDL cholesterol levels (p<0.050). These findings elucidate the varied distribution of cardiometabolic risk factors within our outpatient population.

Now, our discussion counts with additional insights from correlation analysis (Table 2), which revealed significant negative associations between Visceral Adiposity Index (VAI) and insulin resistance parameters (insulin: ρ=-0.167, p=0.006; HOMA-IR: ρ=-0.163, p=0.007) in the total sample, indicating stronger relationships with metabolic health markers. Notably, these associations were more pronounced among men, emphasizing sex-specific disparities in visceral adiposity and metabolic outcomes.

Table 2 presents the correlation coefficients of VAI with various study variables, highlighting significant associations with insulin and HOMA-IR in the total sample and stratified by sex. These findings underscore the differential impact of metabolic and anthropometric variables on VAI, suggesting potential avenues for targeted intervention in cardiometabolic health.

Moreover, analysis across VAI quartiles (Table 4) demonstrated significant differences in neck circumference and systolic blood pressure (p<0.050), reflecting varying levels of visceral adiposity and their implications for cardiovascular risk factors within our cohort.

In conclusion, our multiple linear regression models (Table 5) revealed no significant predictive effects of study variables on VAI after adjusting for sex and age. These findings underscore the complex interactions influencing visceral adiposity levels and highlight the need for further exploration into additional factors influencing cardiometabolic health.

We invite the reviewer to revisit our results, now enriched with these specific findings, which contribute significantly to understanding the nuanced relationships between visceral adiposity and cardiometabolic health markers in our outpatient population.

Reviewer Comment 2: "It must be highlighted that men are much older than women."

Response: We acknowledge the age disparity between men and women in our study cohort. This demographic difference was considered during data analysis and interpretation, ensuring that sex-specific variations in cardiovascular risk factors were appropriately addressed in our findings.

Reviewer Comment 3: "The race of patients is not declared, which might affect the significance of results. Also, exploring fertility age compared with menopausal age would have been critical for interpreting findings in women."

Response: While ethnicity data were not explicitly captured in our study, we recognize its potential impact on cardiovascular risk factors and will address this limitation in future research. Regarding menopausal status, this is an important consideration that warrants further investigation to better understand its influence on VAI and cardiovascular health outcomes in women. We will also address this limitation in future research.

Reviewer Comment 4: "Pearson analysis was not adjusted for confounding factors such as concomitant diseases or therapies and age, both for men and women. Exploring the impact of menopausal state in women could strengthen the study."

Response: We appreciate this critique and agree that adjusting for confounding factors like comorbidities and therapies, along with age stratification, would provide deeper insights into the associations observed. Future studies will incorporate these adjustments to refine the predictive significance of VAI in cardiovascular risk assessment, particularly in relation to menopausal status among women.

Reviewer Comment 5: "A marker of cardiovascular risk might improve the significance of the study to explore the predictive significance of VAI. Discussion relies heavily on speculative interpretations from other studies, potentially reducing the originality of the presented study."

Response: To enhance the predictive significance of our findings, future research will explore additional cardiovascular risk markers in conjunction with VAI. We recognize the need to minimize speculative discussions and focus on presenting original insights derived from our cohort-specific analyses, thereby strengthening the contribution of our study to the existing literature on personalized cardiovascular risk assessment.

Reviewer Comment 6: "Discussion is too much speculative and funded on studies performed by other authors, giving to many details of their researches, and reducing, then, originality of the presented study.''

Response: 

We appreciate the insightful feedback regarding the discussion section of our manuscript. We have taken your comments seriously and have made significant revisions to enhance the originality of our study findings. Specifically, we have reduced the reliance on external studies and focused more on our own data and interpretations (please, see Lines 271-304).

Our revised discussion now emphasizes the unique aspects of our study results, particularly the detailed analysis of cardiometabolic health markers within our outpatient population. By prioritizing our findings and minimizing extensive references to external research, we aim to underscore the novelty and significance of our contributions to the field.

We believe these adjustments have strengthened the manuscript's originality and relevance, offering a clearer and more focused discussion that highlights the specific insights derived from our study data. We look forward to your reconsideration of our revised discussion section.

Once again, we express our gratitude for your thorough review and constructive feedback. Your insights will undoubtedly strengthen the impact of our research. We look forward to your consideration of our revised manuscript.

Reviewer 3 Report

Comments and Suggestions for Authors

Within a cross-sectional study, the authors wanted to investigate the influence of neck circumference (NC), blood pressure (BP), C-reactive protein (CRP), and insulin resistance on the Visceral Adiposity Index (VAI) among 268 cardiologic outpatients (152 men, 116 women).

The VAI integrates anthropometric (waist circumference and BMI) and metabolic (triglyceride and HDL cholesterol levels) parameters, and provides a more comprehensive assessment of visceral fat distribution than traditional measures alone.

As a result, men showed significantly higher VAI values than women, with robust correlations between VAI and markers of insulin resistance. Analysis across VAI quartiles highlighted distinct patterns, revealing lower NC and higher SBP values in higher VAI categories. Multiple linear regression controlling for age and sex showed limited predictive capacity of NC, BP, CRP, and lipid profiles on VAI.

The authors conclude that these findings underscore sex-specific disparities and suggest that VAI serves as a modest yet valuable tool in assessing visceral adiposity and associated cardiovascular risks.

Generally, the manuscript is simply too long. There is a lot of redundance in all sections. Introduction, Methods, Results and Discussion can be shortened without loss of content. The section Conclusion and Future Directions takes itself more than a page.

In the Introduction section, please focus on the aim of the study.

In the Results section, please refer to significant results only. Otherwise, refer to the table.

In the Discussion section, in the first half, results are mainly repeated. Please summarize the significant results briefly and discuss these results more deeply. For example: You found correlations between VAI and IR, and VAI HOMA-IR just for men and the overall cohort, not for women. Why is this? On the other hand, there is a correlation between VAI and SBP/DBP for the overall cohort and women, not for men. Why is this? Are the cardiometabolic risk factors differently distributes between men and women?

Comments on the Quality of English Language

Grammar and style of the manuscript should be carefully edited.

Author Response

RESPONSE TO REVIEWERS' COMMENTS 

 

Manuscript number: endocrines-3022410

 

"Exploring the Associations of Neck Circumference, Blood Pressure, CRP, and Insulin Resistance on the Visceral Adiposity Index: Insights from a Cross-Sectional Study"

 

 

The authors of this document extend their heartfelt gratitude to the Editor-in-Chief and the reviewer for their insightful evaluation of this manuscript. The authors have diligently implemented the suggestions provided by the Editor-in-Chief and the reviewer, leading to a substantial improvement in the overall quality of this work. Noteworthy revisions have been made, and these changes are visually emphasized using the Microsoft Word Track Revisions Tool. A detailed and comprehensive response to each comment is presented in a "point-by-point" format below.

 

 

REVIEWER #3

 

General Comments

 

General Comment #1:

Within a cross-sectional study, the authors wanted to investigate the influence of neck circumference (NC), blood pressure (BP), C-reactive protein (CRP), and insulin resistance on the Visceral Adiposity Index (VAI) among 268 cardiologic outpatients (152 men, 116 women). The VAI integrates anthropometric (waist circumference and BMI) and metabolic (triglyceride and HDL cholesterol levels) parameters, and provides a more comprehensive assessment of visceral fat distribution than traditional measures alone. As a result, men showed significantly higher VAI values than women, with robust correlations between VAI and markers of insulin resistance. Analysis across VAI quartiles highlighted distinct patterns, revealing lower NC and higher SBP values in higher VAI categories. Multiple linear regression controlling for age and sex showed limited predictive capacity of NC, BP, CRP, and lipid profiles on VAI. The authors conclude that these findings underscore sex-specific disparities and suggest that VAI serves as a modest yet valuable tool in assessing visceral adiposity and associated cardiovascular risks.

Response:

Dear Erudite Reviewer, thank you so much for your time and expertise while reviewing our manuscript. We appreciate your valuable contributions to the peer review process. We imposed the comments you kindly suggested on our manuscript. As a sign of utmost respect, we provide a point-by-point response to your comments below. Thank you once again for reviewing our work. After addressing your comments, a significantly improved version of the article emerged, and we are proud to resubmit the improved version to Endocrines for your reevaluation.

 

Major Comments

Major Comment #1:

Generally, the manuscript is simply too long. There is a lot of redundance in all sections. Introduction, Methods, Results and Discussion can be shortened without loss of content. The section Conclusion and Future Directions takes itself more than a page.

Response:

Dear Erudite Reviewer, after rereading our manuscript and reading your precious comment, we must agree that the manuscript is long. In order to improve the manuscript length based on your suggestion, we reduced the manuscript sections' content, focusing on the key aspects. We use the Microsoft Word Track Revisions tool to mark the abbreviations throughout all sections and facilitate your reevaluation of the manuscript's length. After this peer review stage, kindly revisit the manuscript's sections to assess their lengths. Thank you once again for your time and experience reviewing our work. Your comments have been instrumental in reshaping it into a better understanding.

 

Major Comment #2:

In the Introduction section, please focus on the aim of the study.

Response:

Dear Erutite Reviewer, we took your comment into severe account and have significantly improved our introduction based on your concern. We now focus on the manuscript’s primary objective. Please kindly revisit our introduction. We used the Microsoft Tracked Changes Tool to facilitate your revision. Thank you once again for your time and patience in reviewing our work. Kindly refer to Lines 46-80 on Page 2 for the new Introduction section. Your comments have been essential in improving our work.

 

Major Comment #3:

In the Results section, please refer to significant results only. Otherwise, refer to the table.

Response:

Dear Erudite Reviewer, thank you for this precious comment. We considered your concern and reshaped the Results section to focus only on significant results. We used the Microsoft Tracked Changes Tool to facilitate your revision. We invite you to revisit our manuscript’s section and see how the Results are now better presented based on your suggestions. Kindly refer to Lines 154-263 on Pages 4-8 for the new Results section. Thank you once again for your time and patience in revising our work. Your comments have improved its quality at higher levels.

 

Major Comment #4:

In the Discussion section, in the first half, results are mainly repeated. Please summarize the significant results briefly and discuss these results more deeply. For example: You found correlations between VAI and IR, and VAI HOMA-IR just for men and the overall cohort, not for women. Why is this? On the other hand, there is a correlation between VAI and SBP/DBP for the overall cohort and women, not for men. Why is this? Are the cardiometabolic risk factors differently distributes between men and women?

Response:

Dear Erudite Reviewer, thank you so much for this improvement. Besides shortening the Discussion section and deleting irrelevant information, we have discussed these nuanced results mentioned above. We used the Microsoft Word Track Revisions Tool to facilitate your review. Kindly refer to Lines 265-372 on Pages 8-10 for the new Discussion section.

 

On behalf of my coauthors, I once again extend my heartfelt gratitude to the knowledgeable Editor-in-Chief and reviewers. Undoubtedly, their insightful suggestions and constructive feedback have significantly enhanced the quality of our manuscript. 

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

  This is a Completely new paper, at least judging from the title

Examining the Correlations between the Visceral Adiposity Index and Various Anthropometric, Biochemical, and Insulin Resistance Parameters in Brazilians: Findings from a Cross-Sectional Study

 

Exploring the Influence of Neck Circumference, Blood Pressure, CRP, and Insulin Resistance on the Visceral Adiposity Index: Insights from a Cross-Sectional Study

 

It would be much better to write “association of Neck circumference”

Why not to use simpler indexes? Does the VAI assure the same discriminating ability of simpler indexes?

Specific points                                                                                                                                        Our findings suggest that while men and women in our study cohort share similar distributions in age, BMI, and waist circumference, sex-specific differences were evident in neck circumference and lipid profiles. Probably the difference in lipid profiles was not fully appreciated before this paper came to light, but for sure the differences in neck circumference, including the existence of the laryngeal prominence, has been known for centuries.

-tables could be better done, as too many details and too much emphasis is placed on means, SD, r, p;

For instance;

Independent variable Dependent variable           B (95% C.I.)                    p-value               R2

HOMA                              VAI                                   -0.075 (-0.217-0.066)

What is the role for constant?

What is the significance of this relationship?

What is R2?

 

The help of a statistician would be greatly appreciated

 

 

 

 

 

 

Author Response

Thank you for providing the opportunity to revise and resubmit our manuscript, titled "Exploring the Influence of Neck Circumference, Blood Pressure, CRP, and Insulin Resistance on the Visceral Adiposity Index: Insights from a Cross-Sectional Study" (Manuscript ID: endocrines-3022410). We appreciate the time and effort that you have invested in evaluating our work. We have carefully considered the feedback provided and have made comprehensive revisions to address each comment. Below, we provide detailed responses to the reviewers’ comments and describe the changes made in the manuscript.

 

Reviewer #1:

 

Comment 1:

It would be much better to write “association of Neck circumference”.

 

Response:

Dear Reviewer, in response to your comment, we have diligently revised the title of our manuscript. You can find the updated title on Page 1, Line 2 of the document. We believe this modification better reflects the content and scope of our work. Thank you for your valuable feedback, which has helped improve the clarity and accuracy of our submission.

 

Comment 2:

Why not to use simpler indexes? Does the VAI assure the same discriminating ability of simpler indexes?

 

Response:

Dear Reviewer, thank you for your insightful comment regarding the use of the Visceral Adiposity Index (VAI) in our manuscript. We appreciate the opportunity to address your concerns.

Using VAI helps mitigate potential confounding factors related to muscle mass. BMI, for instance, cannot differentiate between muscle and fat, which can lead to misclassification of individuals with high muscle mass as overweight or obese. VAI, by considering metabolic parameters, reduces this limitation, providing a clearer picture of adiposity-related health risks.

Furthermore, the decision to use VAI was based on its comprehensive assessment capabilities. VAI integrates both anthropometric (waist circumference and BMI) and metabolic parameters (triglycerides and HDL cholesterol), providing a more holistic measure of visceral adiposity and its metabolic implications compared to simpler indexes like BMI or waist circumference alone. This comprehensive nature allows for a more nuanced assessment of insulin resistance and cardiovascular risk.

Moreover, research has shown that VAI has superior discriminatory power for identifying cardiometabolic risk factors compared to simpler indexes. Studies have demonstrated that VAI is more strongly associated with insulin resistance, type 2 diabetes, and cardiovascular events than BMI or waist-to-hip ratio. This suggests that VAI can more accurately reflect underlying metabolic disturbances, offering a more robust and reliable metric for our analysis.

By utilizing VAI, we aim to ensure that our study captures the complexity of visceral adiposity and its related health risks, thereby providing a more detailed and accurate assessment than simpler indexes. Thank you for your valuable feedback, which has allowed us to clarify the rationale behind our choice.

 

Comment 3:

Tables could be better done, as too many details and too much emphasis is placed on means.

 

Response:

Dear Reviewer, thank you for your feedback regarding the presentation of our tables. We appreciate your perspective and would like to address your concerns.

The tables in our manuscript were meticulously designed by a highly experienced statistician with over 30 years of expertise in the field. The detailed presentation, including the emphasis on means, was chosen to provide a comprehensive view of our data and ensure clarity in the interpretation of our results.

We believe that providing detailed statistical summaries, including means, enhances the reader's understanding of the central tendencies and variability within our data. This level of detail is crucial for accurately conveying the significance and robustness of our findings.

Thank you once again for your constructive feedback.

 

Comment 4:

What is the role for constant?

 

Response:

Dear Reviewer, thank you for your comment regarding the role of the constant in our multiple linear regression analysis as presented in Table 5.

 

The constant, or intercept, in our regression models serves as the expected value of the dependent variable (VAI) when all independent variables are zero. While some of the constants in our models have high p-values, indicating they are not statistically significant, their inclusion is crucial for several reasons.

Firstly, the constant provides a baseline reference point for interpreting the coefficients of the independent variables. It ensures that we understand the effect of each predictor variable on VAI relative to this baseline, even if the constant itself is not significant.

Secondly, excluding the constant could lead to biased estimates of the coefficients and misinterpretation of the relationships under study. Its inclusion ensures the completeness and accuracy of our regression models.

Although the high p-values suggest that these constants are not significantly different from zero, their presence does not detract from the overall analysis. Rather, it strengthens the integrity of the model by providing a clear framework for interpreting the effects of the independent variables on VAI.

We appreciate your feedback on this matter, and we hope this explanation clarifies the role and importance of the constant in our regression analysis.

 

Comment 5:

What is the significance of this relationship?

 

Response:

Dear Reviewer, thank you for your inquiry regarding the significance of the relationships presented in Table 5 of our manuscript.

The relationships highlighted in Table 5 are derived from multiple linear regression analyses examining the impact of various independent variables on VAI (Visceral Adiposity Index), while controlling for sex and age. Each row in the table represents a separate regression model where VAI is the dependent variable, and different metabolic or anthropometric variables are tested as independent predictors.

The significance of these relationships lies in their ability to elucidate how changes in each independent variable (such as neck circumference, blood pressure, lipid profiles, and glycemic markers) relate to variations in VAI. Although some coefficients may not reach statistical significance (as indicated by their p-values), the overall analysis provides valuable insights into potential associations between these variables and visceral adiposity.

By examining these relationships, our study contributes to a deeper understanding of the factors influencing VAI, a measure linked to cardiometabolic health and insulin resistance. Even non-significant relationships provide context and contribute to the broader picture of metabolic interactions.

The results indicate that several variables, including neck circumference (p = 0.628), systolic blood pressure (p = 0.795), diastolic blood pressure (p = 0.658), C-reactive protein (p = 0.962), total cholesterol (p = 0.587), LDL cholesterol (p = 0.416), HbA1C (p = 0.671), fasting blood glucose (p = 0.821), insulin levels (p = 0.774), and HOMA-IR (p = 0.709), show minimal to negligible effects on VAI in our study cohort. Many of these relationships are not statistically significant, suggesting that in our specific population, these factors may not significantly influence VAI levels when adjusted for sex and age.

These findings provide valuable insights into the complex interplay between metabolic and anthropometric variables and visceral adiposity. While our study highlights potential associations, it also underscores the need for further research to better understand the determinants of VAI and their clinical implications.

We appreciate your interest in this aspect of our research and welcome any further questions or suggestions you may have.

 

Comment 6:

What is R2?

 

Response:

Dear Reviewer, thank you for your question regarding R2 as mentioned in our manuscript. R2, or the coefficient of determination, is a statistical measure that indicates the proportion of the variance in the dependent variable (in this case, VAI or Visceral Adiposity Index) that is explained by the independent variables included in the regression model.

In Table 5, each regression model reports an R2 value, which ranges from 0.001 to 0.011. These R2 values represent the proportion of variability in VAI that is accounted for by the independent variables (such as neck circumference, blood pressure, lipid profiles, etc.) and other factors included in each respective model.

A higher R2 indicates that a larger proportion of the variance in VAI can be explained by the independent variables in the model. Conversely, a lower R2 suggests that the model may not fully capture all the factors influencing VAI, indicating potential for additional variables or factors to be considered.

We hope this explanation clarifies the meaning and significance of R2 in our regression analyses. Please let us know if you have any further questions or if there is anything else we can provide to assist with your review.

 

Comment 7:

The help of a statistician would be greatly appreciated

 

Response:

Dear Reviewer, thank you for your suggestion regarding the involvement of a statistician in our study. We greatly appreciate your feedback.

We want to assure you that our statistical analyses, including the multiple linear regression models presented in Table 5, were conducted with the assistance of a highly experienced statistician. This individual has more than 30 years of expertise in statistical analysis, ensuring that our methods and interpretations are robust and reliable.

His guidance was instrumental in designing the study, selecting appropriate statistical tests, and interpreting the results accurately. We are confident that the statistical approach employed in our manuscript adheres to best practices and provides a solid foundation for our findings.

If you have any specific concerns or suggestions related to the statistical methods used, we would be more than happy to address them in detail. Your feedback is invaluable to us as we strive to present our research in the most rigorous and transparent manner.

Thank you once again for your thoughtful consideration of our work.

 

Final response:

We believe that the revisions have significantly strengthened our manuscript and have addressed all the concerns raised by the reviewers. We hope that the changes we have made are satisfactory and that our manuscript is now suitable for publication in Endocrines.

Thank you once again for your time and consideration. We look forward to your positive response.

Reviewer 2 Report

Comments and Suggestions for Authors

At least one phrase for introduction of the study should be exposed in the abstract.

Explanation of VAI should be furnished in the abstract.

Im-pact (?) line 44

English language should be improved

Variable values should not duplicate in text and tables. Moreover, the results by Gu (ref.20),Pekgor et al. (ref.21) and Jafari (ref. 22) should not reported in numbers in text but only as synthetic main highlighted findings.

Pekgor et al. (ref.21) and Jafari (ref. 22) should not reported in numbers in text but only as synthetic main highlighted findings.

The same for Jabłonowska-Lietz (ref.24) Goldani (ref. 25) Schuster (ref.26). Authors should compare their results with those presented by the aforementioned researchers to highlight their novel findings and their contribution to the studies on validation and clinical use of VAI. Otherwise they have definitively declare that their study is only  confirmatory.

Moreover, the paper remains mainly speculative and projected primarily in future purposes

 

Comments on the Quality of English Language

English language should be more fluent

Author Response

Thank you for providing the opportunity to revise and resubmit our manuscript, titled "Exploring the Influence of Neck Circumference, Blood Pressure, CRP, and Insulin Resistance on the Visceral Adiposity Index: Insights from a Cross-Sectional Study" (Manuscript ID: endocrines-3022410). We appreciate the time and effort that you have invested in evaluating our work. We have carefully considered the feedback provided and have made comprehensive revisions to address each comment. Below, we provide detailed responses to the reviewers’ comments and describe the changes made in the manuscript.

 

Reviewer #2:

 

Comment 1:

At least one phrase for introduction of the study should be exposed in the abstract.

 

Response:

Dear Reviewer, thank you for your feedback regarding the abstract of our study.

We appreciate your suggestion to include at least one phrase introducing the study in the abstract. We ensured that the revised abstract reflected a clear and concise introduction that encapsulated the core focus and significance of our research. Please, find the new abstract within Page 1, Lines 24-34.

Thank you once again for your constructive feedback.

 

 

Comment 2:

Explanation of VAI should be furnished in the abstract.

 

Response:

Dear Reviewer, thank you for your insightful feedback on the abstract of our study. We appreciate your suggestion to include an introductory phrase and an explanation of the Visceral Adiposity Index (VAI) to enhance clarity and context. In response, we have revised the abstract to incorporate a concise introduction that encapsulates the core focus and significance of our research, along with an explanation of VAI. The updated abstract can be found on Page 1, Lines 24-34.

We value your constructive input and eagerly await your further guidance.

 

Comment 3:

Im-pact (?) line 44

 

Response:

Dear Reviewer, thank you for bringing this to our attention. We have rectified the error mentioned in "Impact" within Line 52 of the manuscript.

 

Comment 4:

English language should be improved.

 

Response:

Dear Reviewer, thank you for your feedback regarding the English language in our manuscript. We want to clarify that our team includes native English speakers from the USA. Nevertheless, we have thoroughly revised the manuscript to ensure clarity and correctness during the revision process.

Please let us know if there are any specific areas that require further attention.

 

Comment 5:

The results by Gu (ref.20), Pekgor et al. (ref.21) and Jafari (ref. 22) should not reported in numbers in text but only as synthetic main highlighted findings. The same for Jabłonowska-Lietz (ref.24) Goldani (ref. 25) Schuster (ref.26). Authors should compare their results with those presented by the aforementioned researchers to highlight their novel findings and their contribution to the studies on validation and clinical use of VAI.

 

Response:

Dear Reviewer, thank you for your thoughtful feedback. We have carefully integrated the recommended changes into our manuscript. Specifically, we have restructured the presentation of findings from the following authors: Gu (ref. 20), Pekgor et al. (ref. 21), Jafari (ref. 22), Jabłonowska-Lietz (ref. 24), Goldani (ref. 25), and Schuster (ref. 26). To facilitate your review, these modifications are highlighted in yellow on pages 9 and 10 of the manuscript.

Their respective contributions are now concisely summarized as key highlighted findings, enhancing clarity and underscoring their significance without the need for numerical details in the text. We appreciate your guidance, which has greatly improved the quality and coherence of our work.

 

Comment 6:

Moreover, the paper remains mainly speculative and projected primarily in future purposes

 

Response:

Dear Reviewer, thank you for your thoughtful evaluation of our manuscript. We respectfully disagree with your assessment that our study remains speculative and projected primarily for future purposes. The results presented in our manuscript demonstrate significant empirical findings regarding cardiometabolic health parameters in a well-defined outpatient population.

Firstly, our study sample of 268 individuals, including 152 men and 116 women, provided robust data on various cardiometabolic indicators such as BMI, waist circumference, blood pressure, and lipid profiles (Tables 1-4). These findings underscore the diverse characteristics influencing cardiometabolic risk profiles within our outpatient cohort.

Secondly, the correlation analysis (Table 2) and Visceral Adiposity Index (VAI) stratification (Tables 3 and 4) revealed clear associations between VAI and key variables such as insulin resistance markers and blood pressure, particularly in men. These correlations, although modest in some cases, contribute significantly to our understanding of visceral adiposity and its implications for cardiovascular health.

Finally, our multiple linear regression analyses (Table 5) controlled for sex and age, further reinforcing the relationships observed. Despite the low R-squared values, which suggest that the included variables collectively explain only a small proportion of VAI variance, the associations with insulin resistance parameters and blood pressure remained noteworthy.

Furthermore, it is essential to acknowledge the population-specific nature of VAI, which reflects the demographic and clinical characteristics of our outpatient cohort. VAI integrates waist circumference, BMI, triglycerides, and HDL cholesterol levels, providing a tailored assessment of visceral adiposity and its metabolic implications within our studied population (Table 3). This approach aligns with recent literature suggesting that VAI's utility may vary across different demographic groups and health conditions, emphasizing its nuanced application in diverse clinical settings. Moreover, the observed associations between VAI and insulin resistance markers in our study underscore its relevance in evaluating metabolic health, particularly in settings characterized by high cardiovascular risk profiles (Table 2). These insights support the validity of VAI as a population-specific tool for assessing visceral adiposity and its implications for cardiometabolic health outcomes.

In conclusion, our manuscript provides concrete empirical evidence rather than speculation, highlighting the intricate relationships between visceral adiposity and cardiometabolic health markers in our outpatient population. We believe these findings contribute substantively to the existing literature on this subject.

We appreciate your consideration of our response.

 

Final response:

We believe that the revisions have significantly strengthened our manuscript and have addressed all the concerns raised by the reviewers. We hope that the changes we have made are satisfactory and that our manuscript is now suitable for publication in Endocrines.

Thank you once again for your time and consideration. We look forward to your positive response.

Reviewer 3 Report

Comments and Suggestions for Authors

The authors considered all my comments and suggestions and improved the manuscript accordingly. I have no further questions or comments.

Author Response

Dear Erudite Reviewer,

Thank you so much for recognizing that we’ve improved our manuscript accordingly.

We are more than happy to receive your final feedback and are eager to anticipate the approval of our manuscript for publication in the important journal Endocrines.

Once again, thank you for your time and expertise.

With best regards,

Lucas

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