COVID-19 Vaccination Prior to SARS-CoV-2 Infection Reduced Risk of Subsequent Diabetes Mellitus: A Real-World Investigation Using U.S. Electronic Health Records

Background Previous studies have indicated a bidirectional correlation between diabetes and SARS-CoV-2 infection. However, no investigation has comprehensively explored the potential of COVID-19 vaccination in reducing the risk of new-onset diabetes mellitus (DM) in infected individuals. Methods In the first cohort, we compared the risk of new-onset DM between 1,562,606 SARS-CoV-2 infected individuals and non-infected individuals using the TrinetX database to validate findings in prior literature. For the second cohort, we identified 83,829 vaccinated and 83,829 unvaccinated COVID-19 survivors from the same period. DM, anti-hyperglycemic drug use, and composite of both were defined as outcomes. We conducted Cox proportional hazard regression analysis for the estimation of hazard ratios (HRs) and 95% confidence intervals (CI). Kaplan-Meier analysis was conducted to calculate the incidence of new-onset DM. Subgroup analyses based on age (18-44, 45-64, 65), sex (female, male), race (White, Black or African American, Asian), and BMI categories (<19.9, 20–29, 30–39, ≥40) , sensitivities analyses and a dose response analysis were conducted to validate the findings. Findings The initial cohort of patients infected with SARS-CoV-2 had a 65% increased risk (HR, 1.65; 95%CI, 1.62-1.68) of developing new-onset DM relative to non-infected individuals. In the second cohort, we observed that vaccinated patients were associated with a 21% lower risk of developing new-onset DM in comparison to unvaccinated COVID-19 survivors (HR, 0.79; 95% CI, 0.73-0.86). Subgroup analyses by gender, age, race, and BMI yielded similar results. These findings were consistent in sensitivity analyses and cross-validation with an independent dataset from TriNetX.