Title: Association between lipid accumulation products and gallstones: an analysis of the
National Health and Nutrition Examination Survey 2017-2020
Version: 3 Date: 02 Sep 2024
Reviewer:  Reda Elwakil
Reviewer's report:
Although this manuscript had been thoroughly revised by three reviewers beforehand, I still
have some comments that need to be addressed:
1- The main objective of the study which is the association between LAP and gall stones was
concluded based on  subjective data from a questionnaire study rather than objective data as
the result of ultrasonography or other imaging methods as CT or MRI which compromises the
result of the study.
2- In the multivariate analysis the authors ignored important variables that have an impact on
gall stones such as hepatic steatosis (NAFLD). Both NAFLD and GS share similar risk factors
leading to the development of each disease. On average, there’s an increase in the prevalence
of gallstones in NAFLD patients, and patients with GS were also more likely to have NAFLD.
There was a prevalence of NAFLD in those with asymptomatic gallstones as well, indicating
that the risk factors are crucial in the development of both (Slouha E, Biput SJ, Kuteyi A, Kalloo
AE, Gorantla VR. Non-alcoholic Fatty Liver Disease and Gallstones: A Systematic Review.
Cureus. 2023 Sep 11;15(9):e45027. doi: 10.7759/cureus.45027. PMID: 37829934; PMCID:
PMC10566311.).
3- Insulin resistance diagnosed by the homeostasis model assessment (HOMA-IR) in non-
diabetic patients has an impact on gall stones occurrence. Korean research studied 118 subjects
with no clinical evidence of diabetes mellitus and serum glucose <126 mg/dL. Compared with
controls (n=89), cases (n=29) had higher levels of serum insulin, glucose, triglyceride levels,
and BMI. In t-test and chi-square test for variables, the association between gallstone disease
and serum insulin, HOMA-IR index, and BMI were statistically significant (p<0.05). In multiple
logistic regression analysis, gallstone disease risk increased with the level of serum insulin
(p=0.024, odds ratio=1.376) and HOMA-IR index (p=0.013, odds ratio=2.006).The authors
suggested that hyperinsulinemia and insulin resistance could be associated with gallstone
formation in individuals without clinical diagnosis of diabetes mellitus and with normal serum
glucose level (Kim JM, Lee HL, Moon W, Koh DH, Lee OY, Yoon BC, Choi HS, Hahm JS, Lee
MH, Lee DH, Ahn YH. [Association between insulin, insulin resistance, and gallstone disease
in Korean general population]. Korean J Gastroenterol. 2007 Sep;50(3):183-7. Korean. PMID:
17885284.)
Title: Association between lipid accumulation products and gallstones: an analysis of the
National Health and Nutrition Examination Survey 2017-2020
Version: 3 Date: 02 Sep 2024
Reviewer:  Reda Elwakil
Reviewer's report:
Although this manuscript had been thoroughly revised by three reviewers beforehand, I still
have some comments that need to be addressed:
1- The main objective of the study which is the association between LAP and gall stones was
concluded based on  subjective data from a questionnaire study rather than objective data as
the result of ultrasonography or other imaging methods as CT or MRI which compromises the
result of the study.
2- In the multivariate analysis the authors ignored important variables that have an impact on
gall stones such as hepatic steatosis (NAFLD). Both NAFLD and GS share similar risk factors
leading to the development of each disease. On average, there’s an increase in the prevalence
of gallstones in NAFLD patients, and patients with GS were also more likely to have NAFLD.
There was a prevalence of NAFLD in those with asymptomatic gallstones as well, indicating
that the risk factors are crucial in the development of both (Slouha E, Biput SJ, Kuteyi A, Kalloo
AE, Gorantla VR. Non-alcoholic Fatty Liver Disease and Gallstones: A Systematic Review.
Cureus. 2023 Sep 11;15(9):e45027. doi: 10.7759/cureus.45027. PMID: 37829934; PMCID:
PMC10566311.).
3- Insulin resistance diagnosed by the homeostasis model assessment (HOMA-IR) in non-
diabetic patients has an impact on gall stones occurrence. Korean research studied 118 subjects
with no clinical evidence of diabetes mellitus and serum glucose <126 mg/dL. Compared with
controls (n=89), cases (n=29) had higher levels of serum insulin, glucose, triglyceride levels,
and BMI. In t-test and chi-square test for variables, the association between gallstone disease
and serum insulin, HOMA-IR index, and BMI were statistically significant (p<0.05). In multiple
logistic regression analysis, gallstone disease risk increased with the level of serum insulin
(p=0.024, odds ratio=1.376) and HOMA-IR index (p=0.013, odds ratio=2.006).The authors
suggested that hyperinsulinemia and insulin resistance could be associated with gallstone
formation in individuals without clinical diagnosis of diabetes mellitus and with normal serum
glucose level (Kim JM, Lee HL, Moon W, Koh DH, Lee OY, Yoon BC, Choi HS, Hahm JS, Lee
MH, Lee DH, Ahn YH. [Association between insulin, insulin resistance, and gallstone disease
in Korean general population]. Korean J Gastroenterol. 2007 Sep;50(3):183-7. Korean. PMID:
17885284.)
Please review this paper.
user
Title: Association between lipid accumulation products and gallstones: an analysis of the
National Health and Nutrition Examination Survey 2017-2020
Version: 3 Date: 02 Sep 2024
Reviewer:  Reda Elwakil
Reviewer's report:
Although this manuscript had been thoroughly revised by three reviewers beforehand, I still
have some comments that need to be addressed:
1- The main objective of the study which is the association between LAP and gall stones was
concluded based on  subjective data from a questionnaire study rather than objective data as
the result of ultrasonography or other imaging methods as CT or MRI which compromises the
result of the study.
2- In the multivariate analysis the authors ignored important variables that have an impact on
gall stones such as hepatic steatosis (NAFLD). Both NAFLD and GS share similar risk factors
leading to the development of each disease. On average, there’s an increase in the prevalence
of gallstones in NAFLD patients, and patients with GS were also more likely to have NAFLD.
There was a prevalence of NAFLD in those with asymptomatic gallstones as well, indicating
that the risk factors are crucial in the development of both (Slouha E, Biput SJ, Kuteyi A, Kalloo
AE, Gorantla VR. Non-alcoholic Fatty Liver Disease and Gallstones: A Systematic Review.
Cureus. 2023 Sep 11;15(9):e45027. doi: 10.7759/cureus.45027. PMID: 37829934; PMCID:
PMC10566311.).
3- Insulin resistance diagnosed by the homeostasis model assessment (HOMA-IR) in non-
diabetic patients has an impact on gall stones occurrence. Korean research studied 118 subjects
with no clinical evidence of diabetes mellitus and serum glucose <126 mg/dL. Compared with
controls (n=89), cases (n=29) had higher levels of serum insulin, glucose, triglyceride levels,
and BMI. In t-test and chi-square test for variables, the association between gallstone disease
and serum insulin, HOMA-IR index, and BMI were statistically significant (p<0.05). In multiple
logistic regression analysis, gallstone disease risk increased with the level of serum insulin
(p=0.024, odds ratio=1.376) and HOMA-IR index (p=0.013, odds ratio=2.006).The authors
suggested that hyperinsulinemia and insulin resistance could be associated with gallstone
formation in individuals without clinical diagnosis of diabetes mellitus and with normal serum
glucose level (Kim JM, Lee HL, Moon W, Koh DH, Lee OY, Yoon BC, Choi HS, Hahm JS, Lee
MH, Lee DH, Ahn YH. [Association between insulin, insulin resistance, and gallstone disease
in Korean general population]. Korean J Gastroenterol. 2007 Sep;50(3):183-7. Korean. PMID:
17885284.)
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