DM and H. pylori infection are widespread globally, presenting significant challenges to public health. This longitudinal study aimed to evaluate the effects of DM and H. pylori infection on all-cause, cardiovascular, and diabetic mortality. In our study, conducted through a nationwide population-based survey and utilizing data from the National Death Registry, we found that the coexistence of DM and H. pylori infection significantly elevates the risk of all-cause, cardiovascular, and diabetic mortality. After adjusting for various confounding factors including age, sex, ethnicity, marital status, family income, education level, BMI, waist circumference, lipid profile, HbA1c, smoking status, and urinary albumin-to-creatinine ratio (UACR), participants with both DM and H. pylori infection exhibited a 1.33-fold increased risk of all-cause mortality, a 1.92-fold increased risk of cardiovascular mortality, and a 15.81-fold increased risk of diabetic mortality compared to those without DM or H. pylori infection.
Diabetes and H. pylori infection pose significant global health challenges due to their widespread occurrence in the general population[18, 19]. Many previous studies have indicated a certain correlation between them. Prior investigations have indicated a heightened prevalence of H. pylori infection among diabetic patients[20]. In a meta-analysis conducted by Feng Wang, which encompassed 39 eligible studies spanning from 1997 to 2012, a notable correlation emerged between H. pylori infection and elevated risks of both T1DM and T2DM[21]. In a study conducted in 2024[22], a noteworthy correlation was identified between H. pylori infection and T1DM ([OR] 1.77, 95% [CI] 1.47–2.12, p < 0.0001). As per the findings of Xin et al., individuals with type 2 diabetes mellitus (T2DM) exhibit a greater risk of H. pylori eradication failure compared to non-diabetic individuals (odds ratio [OR] = 2.59, 95% confidence interval [CI] 1.82–3.70)[23]. In addition to a higher prevalence of Helicobacter pylori infection in diabetic patients, H. pylori infection can also lead to elevated glycated hemoglobin levels, thereby contributing to an increased incidence of diabetes. A study conducted in 2023 revealed that compared to the persistent Helicobacter pylori infection-negative group, individuals in the persistent H. pylori infection and new infection groups exhibited significantly higher levels of HbA1c (p < 0.05). Conversely, HbA1c levels decreased following H. pylori eradication[24]. Another study conducted in 2019[25] found that patients with Helicobacter pylori infection exhibited significantly higher levels of glycated hemoglobin A compared to those without infection (WMD = 0.50, 95% CI: 0.28–0.72, p < 0.001). Subgroup analysis based on diabetes subtype demonstrated a correlation between Helicobacter pylori infection and increased glycated hemoglobin A levels in both type 1 diabetes (p < 0.001, 95% CI: 0.12–0.80) and type 2 diabetes (p < 0.001, 95% CI: 0.28–0.90).
There are several underlying mechanisms that could elucidate the association between H. pylori infection and diabetes. Firstly, H. pylori infection initiates the production of proinflammatory cytokines, potentially disrupting glycemic control[26]. Secondly, emerging evidence supports the notion that inflammation may play a pivotal role in the pathogenesis of type 2 diabetes, akin to an autoinflammatory disorder. This process involves inflammatory cytokines inducing the phosphorylation of serine residues on the insulin receptor substrate, impeding its interaction with insulin receptors and compromising insulin function[22, 27]. Thirdly, H. pylori infection-induced inflammation can impact pancreatic β cells, leading to reduced insulin secretion. Notably, cag + strains of H. pylori may exacerbate this effect by influencing somatostatin production[28]. Moreover, research indicates that H. pylori can promote insulin resistance by inducing chronic inflammation and modulating insulin regulation of gastrointestinal hormones[29]. Additionally, gastritis caused by H. pylori may disrupt the secretion of gastric-related hormones such as leptin, growth hormone-releasing hormone, gastrin, and somatostatin, potentially affecting susceptibility to diabetes[30, 31]. Furthermore, studies have reported a positive correlation between H. pylori infection and impaired insulin secretion. Lastly, compromised nonspecific immunity in diabetic patients may increase the risk of H. pylori infection. The mechanisms proposed above elucidate the potential link between H. pylori infection and the risk of diabetes. Furthermore, the impact of Helicobacter pylori infection on blood glucose and diabetes may outweigh the influence of blood glucose levels on H. pylori presence. This observation clarifies why, in our study, although patients in the DM+/HP + group exhibited a higher risk of all-cause mortality, diabetes-related mortality, and CVD mortality compared to those in the DM−/HP − group, the simultaneous occurrence of diabetes and H. pylori infection presented the most pronounced elevation in the risk of diabetes-related mortality. While a synergistic effect between the two diseases is plausible, further extensive research is required to substantiate these findings.
Our study holds a unique advantage as it is the first cohort investigation to delineate long-term mortality trends among populations with diabetes and H. pylori status. This analysis was conducted utilizing a representative population-based database, thereby enhancing the robustness of our findings. The conclusions of this study align with previous research findings, offering valuable insights into the eradication treatment of Helicobacter pylori in patients with diabetes. To control for potential confounding effects of various covariates, this study designed models to adjust for confounding factors, thereby enhancing the reliability of the results.
This study had several limitations. Firstly, the present study exclusively utilized data from the NHANES database population, limiting the generalizability of the results to populations worldwide. Secondly, due to the lack of specific data in the NHANES database, the study could not differentiate between types of diabetes (type 1 or type 2). Therefore, it was not possible to separately analyze the effects of H. pylori infection on mortality in patients with type 1 or type 2 diabetes. Thirdly, cross-sectional studies do not establish causality. To elucidate causality further, additional prospective cohort studies and randomized controlled trials are warranted.