Title: A negative correlation of low estimated glucose disposal rate with significant liver fibrosis
in adults with NAFLD and obesity: results from NHANES 2017–2020
Version: 2 Date: 20 Feb 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-While the study aims to investigate the relationship between eGDR and liver fibrosis, the exact
rationale for focusing specifically on BMI groups (normal weight, overweight, and obesity)
could be elaborated more. While BMI is a relevant factor in NAFLD, further justification on
why stratifying by BMI is critical for understanding the role of eGDR in fibrosis might enhance
the clarity of the research focus.
-The importance of insulin resistance (IR) markers is well stated in the introduction, but the
connection between insulin resistance, obesity, and fibrosis progression could be explored
further. More details on how eGDR interacts with other metabolic pathways in NAFLD could
provide a clearer foundation for why eGDR might be an effective marker in these patients.
-The study mentions important covariates such as BMI, waist circumference, and hypertension
but doesn’t discuss whether other factors (e.g., diet, physical activity, liver enzyme levels beyond
ALT and AST, medication use, etc.) could influence both eGDR and fibrosis progression.
Addressing additional potential confounders in the analysis would enhance the robustness of
the study.
-While the exclusion of certain individuals (e.g., pregnant women, heavy drinkers, missing
data) is justified, the rationale for excluding individuals with CAP < 248 dB/m is not fully
explained. Why this cut-off value for CAP was chosen could be clarified, as this may influence
the generalizability of the findings to broader NAFLD populations, especially those with less
severe disease.
-Additionally, the exclusion of heavy drinkers is mentioned, but the potential overlap between
alcohol-related liver damage and NAFLD could be addressed to reinforce the decision to exclude
these individuals.
-While the authors suggest that insulin resistance (IR) plays a role in liver fibrosis progression,
the discussion could benefit from a more detailed exploration of the potential mechanisms
underlying this relationship. Specifically, the pathophysiology of how eGDR may influence
fibrosis could be expanded. Are there inflammatory pathways involved? Does eGDR correlate
with other biomarkers of liver injury or inflammation? Providing more insight into the biological
underpinnings would strengthen the narrative.
-The discussion briefly mentions the relationship between CRP, WBC, and liver fibrosis but does
not thoroughly explore how other confounding factors, such as medications, diet, or comorbid
conditions (e.g., hypertension, diabetes), might influence both eGDR and fibrosis progression.
These confounders could play an important role, and discussing them more thoroughly would
give the study additional depth.
-The authors mention that FibroScan was used to measure liver stiffness and that this introduces
potential diagnostic bias. While this is a fair point, the authors could further elaborate on
the limitations of FibroScan as a diagnostic tool (e.g., its sensitivity in individuals with
severe obesity or technical limitations in certain patient populations). This would help readers
understand the potential challenges of relying solely on non-invasive tests.
Title: A negative correlation of low estimated glucose disposal rate with significant liver fibrosis
in adults with NAFLD and obesity: results from NHANES 2017–2020
Version: 2 Date: 20 Feb 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-While the study aims to investigate the relationship between eGDR and liver fibrosis, the exact
rationale for focusing specifically on BMI groups (normal weight, overweight, and obesity)
could be elaborated more. While BMI is a relevant factor in NAFLD, further justification on
why stratifying by BMI is critical for understanding the role of eGDR in fibrosis might enhance
the clarity of the research focus.
-The importance of insulin resistance (IR) markers is well stated in the introduction, but the
connection between insulin resistance, obesity, and fibrosis progression could be explored
further. More details on how eGDR interacts with other metabolic pathways in NAFLD could
provide a clearer foundation for why eGDR might be an effective marker in these patients.
-The study mentions important covariates such as BMI, waist circumference, and hypertension
but doesn’t discuss whether other factors (e.g., diet, physical activity, liver enzyme levels beyond
ALT and AST, medication use, etc.) could influence both eGDR and fibrosis progression.
Addressing additional potential confounders in the analysis would enhance the robustness of
the study.
-While the exclusion of certain individuals (e.g., pregnant women, heavy drinkers, missing
data) is justified, the rationale for excluding individuals with CAP < 248 dB/m is not fully
explained. Why this cut-off value for CAP was chosen could be clarified, as this may influence
the generalizability of the findings to broader NAFLD populations, especially those with less
severe disease.
-Additionally, the exclusion of heavy drinkers is mentioned, but the potential overlap between
alcohol-related liver damage and NAFLD could be addressed to reinforce the decision to exclude
these individuals.
-While the authors suggest that insulin resistance (IR) plays a role in liver fibrosis progression,
the discussion could benefit from a more detailed exploration of the potential mechanisms
underlying this relationship. Specifically, the pathophysiology of how eGDR may influence
fibrosis could be expanded. Are there inflammatory pathways involved? Does eGDR correlate
with other biomarkers of liver injury or inflammation? Providing more insight into the biological
underpinnings would strengthen the narrative.
-The discussion briefly mentions the relationship between CRP, WBC, and liver fibrosis but does
not thoroughly explore how other confounding factors, such as medications, diet, or comorbid
conditions (e.g., hypertension, diabetes), might influence both eGDR and fibrosis progression.
These confounders could play an important role, and discussing them more thoroughly would
give the study additional depth.
-The authors mention that FibroScan was used to measure liver stiffness and that this introduces
potential diagnostic bias. While this is a fair point, the authors could further elaborate on
the limitations of FibroScan as a diagnostic tool (e.g., its sensitivity in individuals with
severe obesity or technical limitations in certain patient populations). This would help readers
understand the potential challenges of relying solely on non-invasive tests.
Please review this paper.
user
Title: A negative correlation of low estimated glucose disposal rate with significant liver fibrosis
in adults with NAFLD and obesity: results from NHANES 2017–2020
Version: 2 Date: 20 Feb 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-While the study aims to investigate the relationship between eGDR and liver fibrosis, the exact
rationale for focusing specifically on BMI groups (normal weight, overweight, and obesity)
could be elaborated more. While BMI is a relevant factor in NAFLD, further justification on
why stratifying by BMI is critical for understanding the role of eGDR in fibrosis might enhance
the clarity of the research focus.
-The importance of insulin resistance (IR) markers is well stated in the introduction, but the
connection between insulin resistance, obesity, and fibrosis progression could be explored
further. More details on how eGDR interacts with other metabolic pathways in NAFLD could
provide a clearer foundation for why eGDR might be an effective marker in these patients.
-The study mentions important covariates such as BMI, waist circumference, and hypertension
but doesn’t discuss whether other factors (e.g., diet, physical activity, liver enzyme levels beyond
ALT and AST, medication use, etc.) could influence both eGDR and fibrosis progression.
Addressing additional potential confounders in the analysis would enhance the robustness of
the study.
-While the exclusion of certain individuals (e.g., pregnant women, heavy drinkers, missing
data) is justified, the rationale for excluding individuals with CAP < 248 dB/m is not fully
explained. Why this cut-off value for CAP was chosen could be clarified, as this may influence
the generalizability of the findings to broader NAFLD populations, especially those with less
severe disease.
-Additionally, the exclusion of heavy drinkers is mentioned, but the potential overlap between
alcohol-related liver damage and NAFLD could be addressed to reinforce the decision to exclude
these individuals.
-While the authors suggest that insulin resistance (IR) plays a role in liver fibrosis progression,
the discussion could benefit from a more detailed exploration of the potential mechanisms
underlying this relationship. Specifically, the pathophysiology of how eGDR may influence
fibrosis could be expanded. Are there inflammatory pathways involved? Does eGDR correlate
with other biomarkers of liver injury or inflammation? Providing more insight into the biological
underpinnings would strengthen the narrative.
-The discussion briefly mentions the relationship between CRP, WBC, and liver fibrosis but does
not thoroughly explore how other confounding factors, such as medications, diet, or comorbid
conditions (e.g., hypertension, diabetes), might influence both eGDR and fibrosis progression.
These confounders could play an important role, and discussing them more thoroughly would
give the study additional depth.
-The authors mention that FibroScan was used to measure liver stiffness and that this introduces
potential diagnostic bias. While this is a fair point, the authors could further elaborate on
the limitations of FibroScan as a diagnostic tool (e.g., its sensitivity in individuals with
severe obesity or technical limitations in certain patient populations). This would help readers
understand the potential challenges of relying solely on non-invasive tests.
assistant