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Home All Specialties Chronic Disease

Obesity is a mediating factor for gallstone disease risk

bySiwen LiuandAlex Chan
July 30, 2025
in Chronic Disease, Gastroenterology, Surgery
Reading Time: 2 mins read
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1. In a retrospective cohort study of adults included in the National Health and Nutrition Examination Survey (NHANES), obesity was associated with increased odds of gallstones.

2. The inflammatory markers white blood cell count (WBC), neutrophil count (NEU), and C-reactive protein (CRP) partially mediated this relationship.

Evidence Rating Level: 2 (Good)

The mechanisms underlying the relationship between obesity and gallstones are unclear. Some studies have suggested that inflammatory factors may mediate the relationship between obesity and gallstones, but evidence is lacking. This study thus examined the relationship between obesity and gallstones and the mediating role of inflammatory factors. This retrospective cohort study analyzed data from the National Health and Nutrition Examination Survey (NHANES) collected between 2017 and 2020 and included adults aged >20 years. The study population was divided into four groups: “Obesity with Gallstones,” “Gallstones without Obesity,” “Obesity without Gallstones,” and “Neither Gallstones nor Obesity.” The presence of gallstones was self-reported, and obesity was defined as a BMI ≥ 30kg/m2. Inflammatory markers included white blood cell count (WBC), neutrophil count (NEU), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), and the systemic immune inflammation index (SII). In total, 7978 were included in the study, of which 517 were in the “Gallstone with obesity” group (mean [SD] age = 56.11 (15.36); female [%] = 401 [77.6]). Obesity was associated with an increased odds of gallstones (adjusted odds Ratio (OR) = 1.86; 95% CI, 1.57–2.22). Inflammatory markers, such as WBC (adjusted OR = 1.61; 95% CI, 1.22–2.11), NEU (adjusted OR = 1.46; 95% CI, 1.17–1.81), and CRP (adjusted OR = 1.18; 95% CI, 1.10–1.28), were also associated with increased odds of gallstones. After adjusting for confounders, WBC, NEU, and CRP mediated the relationship between obesity and gallstones by 3.91%, 3.76%, and 12.48%, respectively. Subgroup analysis found only WBC and NEU to mediate effects in individuals 41–60 years, while PLR had a negative association in those over 60. Among females, no mediating effects were found after adjustments. Overall, this study found obesity to increase the risk of gallstones, with some inflammatory markers partially mediating this relationship. Reducing inflammation may help lower the risk of gallstone formation associated with obesity. Future studies are needed to confirm these findings. 

Click to read the study in EJMR

Image: PD

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