Title: Association between glycated hemoglobin/high-density lipoprotein ratio and
nonalcoholic fatty liver disease in a U.S. nondiabetic population: a cross-sectional study based
on NHANES 2017-2020 data
Version: 1 Date: 29 Jun 2025
Reviewer's report:
The authors have adequately addressed most of my previous comments. However, the major
concern—the explanation of the non-linear association and the inflection point at a ratio of 1.43
—remains unresolved.
In particular, for HbA1c/HDL-C ratios below 1.043, the data appear counterintuitive. For
example, as shown in the figure 2 ( the main finding), patients with a ratio of 0.5 seem to have a
higher risk of NAFLD than those with a ratio of 1.0. This contradicts the general understanding
that a lower HbA1c and higher HDL-C (i.e., a lower ratio) typically indicate better metabolic
health.
The authors’ discussion—“At ratios below this inflection point, HbA1c/HDL-C was negatively
associated with NAFLD, suggesting that moderately higher ratios in this interval are instead
associated with a decreased risk of NAFLD. This trend may reflect a relatively healthy metabolic
state, i.e., good glycemic control (low HbA1c) and high HDL-C levels, when insulin sensitivity
is enhanced, hepatic lipid metabolism is balanced, and inflammation is low, which helps to
reduce hepatic lipid deposition.”—does not seem to adequately explain this paradox.
Title: Association between glycated hemoglobin/high-density lipoprotein ratio and
nonalcoholic fatty liver disease in a U.S. nondiabetic population: a cross-sectional study based
on NHANES 2017-2020 data
Version: 1 Date: 29 Jun 2025
Reviewer's report:
The authors have adequately addressed most of my previous comments. However, the major
concern—the explanation of the non-linear association and the inflection point at a ratio of 1.43
—remains unresolved.
In particular, for HbA1c/HDL-C ratios below 1.043, the data appear counterintuitive. For
example, as shown in the figure 2 ( the main finding), patients with a ratio of 0.5 seem to have a
higher risk of NAFLD than those with a ratio of 1.0. This contradicts the general understanding
that a lower HbA1c and higher HDL-C (i.e., a lower ratio) typically indicate better metabolic
health.
The authors’ discussion—“At ratios below this inflection point, HbA1c/HDL-C was negatively
associated with NAFLD, suggesting that moderately higher ratios in this interval are instead
associated with a decreased risk of NAFLD. This trend may reflect a relatively healthy metabolic
state, i.e., good glycemic control (low HbA1c) and high HDL-C levels, when insulin sensitivity
is enhanced, hepatic lipid metabolism is balanced, and inflammation is low, which helps to
reduce hepatic lipid deposition.”—does not seem to adequately explain this paradox.
Please review this paper.
user
Title: Association between glycated hemoglobin/high-density lipoprotein ratio and
nonalcoholic fatty liver disease in a U.S. nondiabetic population: a cross-sectional study based
on NHANES 2017-2020 data
Version: 1 Date: 29 Jun 2025
Reviewer's report:
The authors have adequately addressed most of my previous comments. However, the major
concern—the explanation of the non-linear association and the inflection point at a ratio of 1.43
—remains unresolved.
In particular, for HbA1c/HDL-C ratios below 1.043, the data appear counterintuitive. For
example, as shown in the figure 2 ( the main finding), patients with a ratio of 0.5 seem to have a
higher risk of NAFLD than those with a ratio of 1.0. This contradicts the general understanding
that a lower HbA1c and higher HDL-C (i.e., a lower ratio) typically indicate better metabolic
health.
The authors’ discussion—“At ratios below this inflection point, HbA1c/HDL-C was negatively
associated with NAFLD, suggesting that moderately higher ratios in this interval are instead
associated with a decreased risk of NAFLD. This trend may reflect a relatively healthy metabolic
state, i.e., good glycemic control (low HbA1c) and high HDL-C levels, when insulin sensitivity
is enhanced, hepatic lipid metabolism is balanced, and inflammation is low, which helps to
reduce hepatic lipid deposition.”—does not seem to adequately explain this paradox.
assistant