Background/Aims: Previous evidence regarding the combined effects of metabolic disorders on intestinal barrier function (IBF) remains limited. We hypothesized that metabolic disorders interact to increase the risk of intestinal barrier dysfunction. Methods: This retrospective case-control study included 4,289 individuals who underwent IBF assessment. Controls with normal biomarker levels were propensity score-matched to cases with abnormal D-lactic acid, diamine oxidase (DAO), or endotoxin. Logistic regression and interaction models were applied to assess associations between metabolic indicators and intestinal barrier dysfunction. Results: Hypertension (odds ratio OR, 1.36; 95% confidence interval CI, 1.20-1.55; P< 0.001), dyslipidemia (OR, 1.70; 95% CI, 1.49-1.96; P< 0.001), and hyperglycemia (OR, 1.80; 95% CI, 1.57-2.08; P< 0.001) were significantly associated with intestinal barrier dysfunction. Subgroup analyses confirmed that dyslipidemia and hyperglycemia were independently associated with elevated DAO, D-lactic acid, and endotoxin levels. Both multiplicative and additive interactions were observed between key metabolic factors. Particularly, dyslipidemia and hyperglycemia showed significant additive interactions (relative excess risk due to interaction, 0.79 95% CI, 0.19-1.35, P= 0.008; attributable proportion due to interaction, 0.29 95% CI, 0.06-0.46, P= 0.008; synergy index, 1.82 95% CI, 1.13-3.41, P= 0.008). When stratified by age and sex, broadly similar trends were observed in participants aged ≥ 50 years and in males. Conclusions: Dyslipidemia and hyperglycemia are associated with intestinal barrier dysfunction and show a synergistic combined effect. Individuals with both should receive prioritized IBF monitoring and early metabolic intervention to protect barrier integrity.
Zhang et al. (Thu,) studied this question.