Causal relationships of Helicobacter pylori and related gastrointestinal diseases on Type 2 diabetes: Univariable and Multivariable Mendelian randomization

PLoS One. 2024 Apr 23;19(4):e0300835. doi: 10.1371/journal.pone.0300835. eCollection 2024.


Background: Previous observational studies have demonstrated a connection between the risk of Type 2 diabetes mellitus (T2DM) and gastrointestinal problems brought on by Helicobacter pylori (H. pylori) infection. However, little is understood about how these factors impact on T2DM.

Method: This study used data from the GWAS database on H. pylori antibodies, gastroduodenal ulcers, chronic gastritis, gastric cancer, T2DM and information on potential mediators: obesity, glycosylated hemoglobin (HbA1c) and blood glucose levels. Using univariate Mendelian randomization (MR) and multivariate MR (MVMR) analyses to evaluate the relationship between H. pylori and associated gastrointestinal diseases with the risk of developing of T2DM and explore the presence of mediators to ascertain the probable mechanisms.

Results: Genetic evidence suggests that H. pylori IgG antibody (P = 0.006, b = 0.0945, OR = 1.0995, 95% CI = 1.023-1.176), H. pylori GroEL antibody (P = 0.028, OR = 1.033, 95% CI = 1.004-1.064), gastroduodenal ulcers (P = 0.019, OR = 1.036, 95% CI = 1.006-1.068) and chronic gastritis (P = 0.005, OR = 1.042, 95% CI = 1.012-1.074) are all linked to an increased risk of T2DM, additionally, H. pylori IgG antibody is associated with obesity (P = 0.034, OR = 1.03, 95% CI = 1.002-1.055). The results of MVMR showed that the pathogenic relationship between H. pylori GroEL antibody and gastroduodenal ulcer in T2DM is mediated by blood glucose level and obesity, respectively.

Conclusion: Our study found that H. pylori IgG antibody, H. pylori GroEL antibody, gastroduodenal ulcer and chronic gastritis are all related to t T2DM, and blood glucose level and obesity mediate the development of H. pylori GroEL antibody and gastroduodenal ulcer on T2DM, respectively. These findings may inform new prevention and intervention strategies for T2DM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Bacterial / blood
  • Chaperonin 60 / genetics
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / genetics
  • Diabetes Mellitus, Type 2* / microbiology
  • Gastritis / complications
  • Gastritis / microbiology
  • Gastrointestinal Diseases / complications
  • Gastrointestinal Diseases / microbiology
  • Genome-Wide Association Study
  • Helicobacter Infections* / complications
  • Helicobacter Infections* / microbiology
  • Helicobacter pylori*
  • Humans
  • Mendelian Randomization Analysis*
  • Obesity / complications
  • Obesity / microbiology
  • Peptic Ulcer / epidemiology
  • Peptic Ulcer / microbiology
  • Risk Factors


  • Antibodies, Bacterial
  • Chaperonin 60

Grants and funding

This study was supported by the National Natural Science Foundation of China (82074426, 82104864, 82204822), Natural Science Foundation of Liaoning Province (2021-BS-215, 2022-MS-25, 2023-MS-13), Liaoning Revitalization Talents Program (XLYC1802014), Key Research and Development Program of Liaoning Province (2017226015), Natural Science Foundation of Tibet Autonomous Region (XZ202301ZR0030G, XZ2023ZR-ZY82(Z)). There was no additional external funding received for this study.