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Risk stratification for proton pump inhibitor-associated type 2 diabetes: a population-based cohort study
  1. Qiangsheng He1,2,
  2. Man Yang3,4,
  3. Xiwen Qin5,6,7,
  4. Die Fan2,
  5. Jinqiu Yuan1,2,3,
  6. Yihang Pan1
  1. 1Big Data Center, Scientific Research Center, The Seventh Affiliated Hospital Sun Yat-sen University, Shenzhen, Guangdong, China
  2. 2Clinical Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
  3. 3Center for Digestive Disease, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China
  4. 4Special Minimally Invasive Surgery Department, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
  5. 5Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Science, Monash University, Melbourne, Victoria, Australia
  6. 6School of Population and Global Health, Faculty of Medicine, Density and Health Sciences, University of Western Australia, Perth, Western Australia, Australia
  7. 7Victorian Heart Institute, Monash University, Melbourne, Victoria, Australia
  1. Correspondence to Professor Jinqiu Yuan, Scientific Research Centre, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518107, Guangdong, China; yuanjq5{at}; Dr Yihang Pan; panyih{at}

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We have recently reported in GUT that regular proton pump inhibitor (PPI) use was associated with a 24% increased risk of type 2 diabetes mellitus (T2DM).1 This was the first study demonstrating an association between PPIs and diabetes. However, all included participants were healthcare professionals and the findings have not been verified in general populations. Additionally, investigation of subgroups at high absolute risk of diabetes among PPI users is still lacking. Because the absolute effects of interventions tend to increase with baseline risk, individualised treatment based on the patients’ underlying risk may confer benefits and reduce harms. Such risk stratification strategy had been applied to select patients for antihypertensive and statin therapy.2 3 In the present study, we conducted a prospective analysis of the UK-Biobank to (1)confirm the association between PPI use and T2DM in general population and (2) to investigate which population groups may have high net risk.

We included participants free of diabetes from the UK Biobank.4 Regular use of PPIs was defined as taking PPIs in most days of week for the last 4 weeks. T2DM cases were identified from different data sources (primary care, hospital admissions, self-report and death register). We evaluated hazard ratios (HRs) adjusting for potential confounders. We calculated the risk difference (RD) based …

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  • QH and MY are joint first authors.

  • Correction notice This article has been corrected since it published Online First. The provenance and peer review statement has been included.

  • Contributors JY had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: JY and YP. Acquisition, analysis or interpretation of data: All authors. Drafting of the manuscript: QH and MY. Critical revision of the manuscript for important intellectual content: all authors. Statistical analysis: JY and QH. Obtained funding: JY and YP. Administrative, technical or material support: JY and YP. Supervision: JY and YP.

  • Funding This work was supported by the startup grant for the 100 Top Talents Program, The Seventh Affiliated Hospital, Sun Yat-sen University (392012), the Youth Program of National Natural Science Foundation of China (82003524) and the National Key Research and Development Program (2018YFA0902801).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; internally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.