Beyond the Stomach: Linking H. pylori Seropositivity to Insulin Resistance (TyG Index) in a Multi-Ethnic High-Risk Population from Southwest China

Background and Aims: Helicobacter pylori infection is associated with systemic inflammation and may contribute to insulin resistance. The triglyceride-glucose (TyG) index serves as a reliable surrogate marker of insulin resistance and is linked to cardiometabolic diseases. However, evidence regarding the association between H. pylori and the TyG index remains inconsistent, especially in multi-ethnic, high-risk populations from China’s southwestern border region. This study aimed to investigate the relationship between H. pylori infection and the TyG index in such a population. We sought to: (1) assess the independent association, (2) characterize dose–response patterns, and (3) identify metabolic modifiers through stratified analyses, in order to elucidate the extra‑gastric metabolic implications of H. pylori infection. Methods: This study analyzed data from 6,998 adults in a multi‑ethnic health‑screening cohort conducted in Wenshan, Southwest China (2020–2024). Helicobacter pylori infection was diagnosed using the ¹⁴C‑urea breath test (cut‑off > 50 DPM). The TyG index was calculated as ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Comprehensive biochemical and metabolic profiles were assessed. We performed univariable and multivariable regression adjusted for key metabolic confounders, examined dose–response relationships using restricted cubic splines, conducted stratified analyses to identify effect modifiers, and applied E‑value sensitivity analysis to evaluate robustness to unmeasured confounding. Results: Among the 6,998 participants from Wenshan, Southwest China, 2,736 (39.1%) were H. pylori -positive. The H. pylori -positive group exhibited a significantly higher TyG index compared to the negative group (8.8 ± 0.7 vs. 8.7 ± 0.7, p < 0.001). In adjusted models, a higher TyG index remained independently associated with H. pylori infection (OR = 1.14, 95% CI 1.06–1.21). Sensitivity analysis using the E‑value indicated that an unmeasured confounder (e.g., BMI) would need to be associated with both exposures by risk ratios of at least 1.54 to fully explain the observed association, supporting its robustness. Other independent risk factors included male sex, advanced age, dyslipidemia, and elevated absolute monocyte count. Conclusion: A higher TyG index is independently associated with an increased risk of H. pylori infection in this health-screening population from China's southwestern border. The TyG index may serve as a simple metabolic biomarker to identify high-risk individuals, aiding targeted screening in similar multi-ethnic groups. Our findings underscore the systemic inflammatory burden of H. pylori and suggest the TyG index as a simple tool for metabolic risk stratification in infected individuals.