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

Previous studies have indicated a bidirectional correlation between diabetes and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, no investigation has comprehensively explored the potential of coronavirus disease 2019 (COVID-19) vaccination to reduce the risk of new-onset diabetes in infected individuals.In the first of 2 cohorts, we compared the risk of new-onset diabetes between individuals infected with SARS-CoV-2 and noninfected individuals (N = 1,562,606) 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. Diabetes, antihyperglycemic drug use, and a composite of both were defined as outcomes. We conducted Cox proportional hazard regression analysis for the estimation of hazard ratios (HRs) and 95% CIs. Kaplan-Meier analysis was conducted to calculate the incidence of new-onset diabetes. Subgroup analyses based on age (18-44, 45-64, ≥65 years), 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.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 diabetes relative to noninfected individuals. In the second cohort, we observed that vaccinated patients had a 21% lower risk of developing new-onset diabetes in comparison with unvaccinated COVID-19 survivors (HR 0.79; 95% CI 0.73-0.86). Subgroup analyses by sex, age, race, and BMI yielded similar results. These findings were consistent in sensitivity analyses and cross-validation with an independent data set from TriNetX.In conclusion, this study validates a 65% higher risk of new-onset diabetes in SARS-CoV-2-infected individuals compared to noninfected counterparts. Furthermore, COVID-19 survivors who received COVID-19 vaccinations experienced a reduced risk of new-onset diabetes, with a dose-dependent effect. Notably, the protective impact of COVID-19 vaccination is more pronounced among the Black/African American population than other ethnic groups. These findings emphasize the imperative of widespread vaccination to mitigate diabetes risk and the need for tailored strategies for diverse demographic groups to ensure equitable protection.