Risk stratification for proton pump inhibitor-associated type 2 diabetes: a population-based cohort study

He, Qiangsheng; Yang, Man; Qin, Xiwen; Fan, Die; Yuan, Jinqiu; Pan, Yihang

doi:10.1136/gutjnl-2020-323816

Cited by 9 publications

(14 citation statements)

References 9 publications

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“…The baseline predicted risks for individual participants were calculated using the established models. Such risk stratification has been used to identify individuals with high risk of PPI-associated type 2 diabetes (He et al, 2020) and stroke (Yang et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…Detailed description of this cohort can be found elsewhere (Sudlow et al, 2015). The UK Biobank has been used to investigate the association between regular use of PPIs and risk of diabetes (He et al, 2020), inflammatory bowel disease (Xia et al, 2021), and mortality (He et al, 2021).…”

Section: Methodsmentioning

confidence: 99%

“…Acid suppressants have a good short-term safety profile. However, cumulating studies showed that the long-term use of these medicines, particularly PPIs, were associated with various adverse health effects, such as fracture, chronic kidney disease, pneumonia, type 2 diabetes, and rheumatoid arthritis (Freedberg et al, 2017;He et al, 2020;Yuan et al, 2020;Yuan J et al, 2021). Recent studies also showed that PPI use was associated with biliary tract diseases, including cholangitis (Min et al, 2019), cholecystitis (Chuang et al, 2019), and bile duct cancer (Xiong et al, 2020;Kamal et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

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Association Between Regular Use of Gastric Acid Suppressants and Subsequent Risk of Cholelithiasis: A Prospective Cohort Study of 0.47 Million Participants

Yang

Xia

et al. 2022

Front. Pharmacol.

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Background: Gastric acid suppressants have a major impact on gut microbiome which in turn, may increase the risk of cholelithiasis, but epidemiological evidence remains unclear. We undertook this research to evaluate the association between regular use of proton pump inhibitors (PPIs) and H2-receptor antagonists (H2RAs) with risk of cholelithiasis.Methods: Prospective cohort study included 477,293 UK residents aged 37–73 years from the UK Biobank. We included the participants reported PPI or H2RA use, and were free of cholelithiasis or cancer. We evaluated hazard ratios (HRs) of regular use of PPIs or H2RAs and risk of cholelithiasis adjusting for demographic factors, lifestyle habits, the presence of comorbidities, use of other medications, and clinical indications.Results: We identified 12,870 cases of cholelithiasis over a median follow-up of 8.1 years. Regular use of PPIs (HR 1.22 95% CI 1.16–1.29) or H2RAs (HR 1.16, 95% CI 1.05–1.28) was associated with an increased risk of cholelithiasis after confounding adjustment. There were no major differences among individual PPIs/H2RAs. The absolute risk of PPI-associated cholelithiasis was increased with the baseline predicted risk evaluated by known environmental and genetic risk factors (Risk differences in the lowest vs. the highest quartile: 1.37 vs. 4.29 per 1,000 person-years).Conclusion: Regular use of PPIs and H2RAs was associated with increased risk of cholelithiasis. Future prospective studies are required to confirm whether the observed associations are casual.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association Between Regular Use of Gastric Acid Suppressants and Subsequent Risk of Cholelithiasis: A Prospective Cohort Study of 0.47 Million Participants

Yang

Xia

et al. 2022

Front. Pharmacol.

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“…Meanwhile, in vivo studies have suggested the promotion of O -GlcNAcylation (such as OGT-transgenic mice) as an effective treatment in mice colitis [ 24 , 27 ]. In contrast to these findings, some studies pointed that the colonic level of O -GlcNAc was increased in CD patients, and suppressing O -GlcNAcylation may protect mice from colitis [ 50 , 51 ]. Collectively, the role of O -GlcNAcylation in gut inflammation of IBD is also not fully clear.…”

Section: Discussionmentioning

confidence: 99%

Traditional herbal formula Wu-Mei-Wan alleviates TNBS-induced colitis in mice by inhibiting necroptosis through increasing RIPK3 O-GlcNAcylation

Shao

Cheng

et al. 2021

Chin Med

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Background Accumulating evidence indicated that necroptosis plays an essential role in the pathogenesis of inflammatory bowel disease (IBD). The O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) of necroptotic signal molecule receptor-interacting serine-threonine kinase 3 (RIPK3) was reported to exert a protective effect in gut inflammation. Our recent study suggested traditional Chinese herbal formula Wu-Mei-Wan (WMW) as an effective prescription in mouse colitis. However, the potential mechanisms are not fully understood. Considering the crucial role of necroptosis in the pathogenesis of IBD, therefore, this study was designed to explain whether the anti-colitis effect of WMW is mediated by modulating necroptosis and its related mechanisms. Methods The protective effects of WMW on colitis have been determined by detecting colitis mice body weight, disease activity index (DAI), survival rate and colon length. Colonic inflammation was examined by inflammatory cells infiltration and local cytokines levels. After then, we measured the levels of necroptosis and O-GlcNAcylation. C O-immunoprecipitation experiments were used to address whether elevated O-GlcNAcylation can inhibit necroptotic signal transduction in the treatment of WMW. Finally, the key enzymes in O-GlcNAcylation: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) were examined and molecular docking analysis was used to determine effective natural compounds in the regulation on OGT and OGA activities. Results Our results showed that WMW significantly improved mice body weight, survival rate and colon length, decreased DAI in TNBS-induced colitis. WMW obviously alleviated colonic inflammatory responses with reduced macrophages, neutrophils infiltration and local IL-1β, IL-6, TNF-α and IFN-γ levels. It was found that WMW increased colonic O-GlcNAcylation level and inhibited the activation of RIPK1, RIPK3 and MLKL. Then, further experiments revealed that WMW enhanced OGT activity and suppressed OGA activity, thereby increasing RIPK3 O-GlcNAcylation and inhibiting the binding of RIPK3 and MLKL, which led to the inhibition of necroptosis. Additionally, docking analysis demonstrated that hesperidin, coptisine and ginsenoside Rb1 may exert a major role in the regulation on OGT and OGA activities by WMW. Conclusion Our work demonstrated that WMW can alleviate TNBS-induced colitis in mice by inhibiting necroptosis through increasing RIPK3 O-GlcNAcylation.

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“…In addition, PPI use has been linked to hypomagnesemia, which could cause endothelial dysfunction by promoting atherosclerosis, inducing inflammation and inhibiting endothelial proliferation (Ferrè et al, 2010;Dousdampanis et al, 2014), which consequently results in the development of CKD (Dousdampanis et al, 2014). In addition, previous studies found that PPI use was associated with the gut microbiota alterations (Jackson et al, 2016) and diabetes (He et al, 2020;Yuan et al, 2021), which in turn may increase the risk of CKD (Dousdampanis et al, 2014;Yang et al, 2018). More research is required to investigate the underlying mechanisms.…”

Section: Figurementioning

confidence: 99%

Effect of proton pump inhibitors on the risk of chronic kidney disease: A propensity score-based overlap weight analysis using the United Kingdom Biobank

Zhang

Jing

et al. 2022

Front. Pharmacol.

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Background: Proton pump inhibitors (PPIs) are widely used and have been linked to kidney diseases. However, the role of PPI use in the development of chronic kidney disease (CKD) remains unclear. We undertook this study to examine the association between PPI use and the subsequent risk of CKD.Methods: This is a prospective analysis of 462,421 participants free of cancer diagnosis or chronic kidney disease from the United Kingdom Biobank. Self-reported PPI use was recorded using an electronic questionnaire and confirmed by a trained staff. Incident CKD was identified based on the medical history. Overlap propensity score weighting with the Cox model was used to calculate the effect of PPI use on CKD risk. The number needed to harm (NNH) was calculated at 5 and 10 years of follow-up.Results: We documented 7,031 cases of CKD over a median follow-up of 8.1 years. Overlap propensity score weighting analysis showed that regular PPI users had a 37% higher risk of CKD incident than non-users (HR 1.37, 95% CI 1.28–1.47). The association persisted across subgroup analyses, different types of PPIs, and several sensitivity analyses. Quantitative bias analysis indicated that the result was robust to unmeasured confounding (E-value 2.08, lower 95% CI 1.88). The NNH was 147.9 and 78.6 for 5 and 10 years of follow-up, respectively. A head-to-head comparison showed that PPI users had a 19% higher risk of CKD than H2RA users (HR 1.19, 95% CI 1.02–1.39).Conclusion: The regular use of PPI is associated with a higher risk of CKD. Healthcare providers should carefully weigh up the potential benefits against the risk in prescribing PPIs, particularly for patients requiring long-term treatment.

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Risk stratification for proton pump inhibitor-associated type 2 diabetes: a population-based cohort study

Cited by 9 publications

References 9 publications

Association Between Regular Use of Gastric Acid Suppressants and Subsequent Risk of Cholelithiasis: A Prospective Cohort Study of 0.47 Million Participants

Association Between Regular Use of Gastric Acid Suppressants and Subsequent Risk of Cholelithiasis: A Prospective Cohort Study of 0.47 Million Participants

Traditional herbal formula Wu-Mei-Wan alleviates TNBS-induced colitis in mice by inhibiting necroptosis through increasing RIPK3 O-GlcNAcylation

Effect of proton pump inhibitors on the risk of chronic kidney disease: A propensity score-based overlap weight analysis using the United Kingdom Biobank

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