Review for 10.1186/s12876-025-03846-7 (2025)

Title: Long-term weight change patterns in American adulthood in relation to gallstones:
evidence from NHANES
Version: 0 Date: 23 Feb 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-Although the introduction provides a solid background on the prevalence and risk factors of
gallstones, a more detailed discussion on the pathophysiology of gallstones could strengthen
the scientific foundation of the study. For instance, a brief mention of the different types of
gallstones (e.g., cholesterol vs. pigment stones) and how obesity may specifically influence their
formation would clarify the biological relevance of weight change patterns.
-The introduction could briefly elaborate on the specific biological or physiological mechanisms
through which obesity might increase the risk of gallstones (e.g., insulin resistance, cholesterol
metabolism, bile acid composition). This would help link the obesity-related pathways more
directly to the study's primary research question.
-The methods mention that missing data were classified as NA and included in the analysis,
which may introduce bias. A more detailed explanation of the approach used to handle missing
data (e.g., multiple imputation vs. simple exclusion or NA classification) could help clarify how
the authors ensured that missing data did not significantly impact the results.
-While the weight change patterns are well-categorized, it would be useful to briefly address how
participants who experienced rapid weight loss or gain (rather than stable changes) might have
been handled. Rapid weight fluctuations could be an important factor in gallstone formation, so
additional clarification on whether such patterns are included in the analysis would be beneficial.
-The study adjusts for several important confounders (e.g., socioeconomic status, smoking,
alcohol, medical history), but there may be other factors worth considering, such as diet quality
or medications (e.g., cholesterol-lowering drugs or oral contraceptives), which may influence
gallstone risk. Including these variables, if available in the NHANES dataset, could add depth
to the analysis.
-The reliance on BMI as the primary measure of obesity may limit the precision of the study's
findings. Although BMI is widely used, it doesn't differentiate between fat and muscle mass,
which could influence gallstone formation differently. Discussing this limitation in the methods
section would be helpful, and if possible, future studies could consider using additional body
composition measures (e.g., waist-to-hip ratio or body fat percentage).
-While the authors mention the cross-sectional nature of the study and the inability to establish
causality, they could strengthen their argument by acknowledging potential confounding factors
in greater detail. For example, factors such as medication use (e.g., lipid-lowering drugs or
hormone therapy) or changes in diet could have influenced weight change patterns and gallstone
risk. Exploring potential confounders further would help clarify the study’s limitations and
strengthen the conclusions.
-The issue of recall bias regarding the self-reported weight data at age 25 and 10 years before
baseline is mentioned, but the discussion could benefit from a deeper exploration of how recall
bias might have impacted the results. Although the authors cite studies showing the validity
of recalled weight data, discussing the potential magnitude of this bias and its implications for
study accuracy would further reassure readers of the robustness of the findings.
-While the discussion does an excellent job linking insulin resistance and metabolic
dysregulation to gallstone formation, there could be more exploration of other potential
mechanisms, such as alterations in bile composition, gallbladder motility, or gut microbiota,
which may also contribute to gallstone risk in individuals with obesity. This would add depth to
the biological explanation and allow for a broader consideration of the physiological pathways
involved.
-The discussion mentions that transitioning from an obese to a non-obese status in adulthood
is less likely. This could be expanded upon by considering how weight loss in later adulthood
(e.g., through medical intervention or lifestyle changes) might still have health benefits in terms
of reducing gallstone risk, even if the transition to non-obesity is challenging. Exploring this
idea could provide a more optimistic perspective on weight loss interventions later in life.