Proton pump inhibitors use and risk of type 2 diabetes mellitus: correlation analysis, prediction model construction, and key genes identification
Abstract
Introduction: Prior cohort studies reported paradoxical results between proton pump inhibitor (PPI) usage and the risk of type 2 diabetes mellitus (T2DM). We investigated the correlation between the use of PPIs and T2DM risk, constructed predictive models, and identified the key genes involved.
Methods: In the correlation analysis, we extracted and analyzed the data from the National Health and Nutrition Examination Survey (NHANES) database and the FDA Adverse Event Reporting System (FAERS) database to examine the relationship between the use of PPIs and T2DM risk. Then, a nomogram was constructed to estimate the T2DM risk probability in patients treated with PPIs by using the optimal predictors identified by the least absolute shrinkage and selection operator and logistic regression methods. Finally, we investigated the key genes modulated by PPI usage in patients with T2DM by combining various bioinformatics techniques such as network pharmacology, difference analysis, and weighted gene co-expression network analysis.
Results: In the NHANES database, regardless of whether PPI usage was merely included or used to adjust for covariates, the binomial regression models indicated a positive correlation between PPI usage and T2DM risk (all p < 0.001). In the FAERS database, the T2DM signal for patients using PPIs was significant (lower limit of the reporting odds ratio was greater than 1). Sex, race, age, educational level, obesity, hypertension, and high cholesterol were…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.
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