A novel corrected anion gap links metabolic acid attack to peptic ulcer disease

Physiological evidence indicates that systemic acid-base balance may be associated with gastric acid secretion, which is a key factor in peptic ulcers disease (PUD). However, the epidemiological relationship of this association with PUD risk remains unclear.

This study investigates a novel corrected anion gap (AG_corr, reflecting metabolic acid load) and bicarbonate (HCO₃^-, reflecting alkaline reserve) in relation to PUD.

This retrospective case-control study analyzed endoscopy-confirmed 64 PUD patients and 541 non-PUD controls with normal hepatic and renal function from a Fujian tertiary hospital (Jan 2023-Jun 2025). The anion gap (AG) was corrected to fully-corrected AG_corr and albumin-corrected AG (ACAG). Four models (A: AG_corr; B: HCO₃^-; C: AG; D: ACAG) were adjusted for sex, age, and Na to study the relationships between AG_corr, ACAG, AG, HCO₃, and PUD. Post-hoc power and sensitivity analysis were conducted.

Model A showed that AG_corr was significantly positively associated with PUD risk (OR = 1.167, 95% CI: 1.050-1.298, P = 0.045), with a high statistical power of 89%. Sensitivity analysis with an expanded control group (n = 1915) confirmed a significant AG_corr-PUD association (OR = 1.138, 95% CI: 1.029-1.259, P = 0.012), with post hoc power of 0.81. The sensitivity analysis with case-control matching for sex and age showed that AG_corr remained significantly associated with PUD (P = 0.020). In contrast, Model C and Model D were both significantly correlated (P < 0.05) but showed poor fit (H-L P < 0.05). However, their statistical power differed, with values of only 0.64 and 0.84, respectively. Model B indicated a negative correlation between PUD and HCO₃^- (OR = 0.894, 95% CI: 0.802-0.996, P = 0.043), but with low statistical power (65%) and instability in sensitivity analysis.

After adjusting for sex, age, and Na, AG_corr remained an independent risk factor for PUD in individuals with normal liver and kidney function. The fully-corrected AG outperformed both ACAG and uncorrected AG. Metabolic non-volatile acid attack may be an important pathogenic mechanism in PUD. HCO₃^- may have a potential protective effect against PUD. The findings contribute to improving PUD care but require further validation in diverse groups.