Cholecystectomy and blood lipid/glucose traits: insights from a population-based cross-sectional and Mendelian randomization study

Objectives: Cholecystectomy is noted for potentially impacting blood lipid/glucose levels, yet causal links remain unclear. Methods: Cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 were employed to explore the relationship between cholecystectomy and blood lipid/glucose traits. Propensity-score matching (PSM) was performed to equalize baseline differences. Genome-wide association study (GWAS) data from the UK Biobank, FinnGen, Global Lipids Genetics Consortium (GLGC), and the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) were analyzed by Mendelian randomization (MR) to infer causality. Combination of MR results was achieved with meta-analysis. Results: Based on the NHANES database, significantly decreased levels of total cholesterol (TC) (P = 0.021), low-density lipoprotein cholesterol (LDL-C) (P = 0.036), high-density lipoprotein cholesterol (HDL-C) (P = 0.017) and augmented triglyceride (TG) (P = 0.021) were found in patients with gallbladder removal after PSM. No difference was observed in fasting glucose, fasting insulin and hemoglobin A1c (HbA1c). In MR analysis, significant associations were found between cholecystectomy and lower TC (P = 0.002), especially LDL-C (P = 0.002) and HDL-C (P = 0.044). No significant associations were observed with TG, fasting glucose, fasting insulin or HbA1c. Conclusions: Cholecystectomy has specific impacts on serum lipid profiles instead of glucose traits.