Glycaemic control is associated with SARS-CoV-2 breakthrough infections in vaccinated patients with type 2 diabetes: an observational study

Abstract Patients with type 2 diabetes (T2D) are characterized by blunted immune responses, which are affected by glycaemic control. Whether glycaemic control influences the response to COVID-19 vaccines and the incidence of SARS-CoV-2 breakthrough infections is unknown. To explore the association between glycaemic control and immune responses or breakthrough infections in patients with T2D after mRNA-BNT162b2 vaccination, we conducted a prospective observational study among healthcare and educator workers with T2D receiving the mRNA-BNT162b2 vaccine in Campania (Italy). Patients were followed for one year (5 visits) after one full vaccination cycle to evaluate immune responses and monitor the incidence of breakthrough infections. The one-year mean of HbA1c values and canonical risk factors were used to estimate their association with breakthrough infections through Cox regression models adjusted for multiple variables. Overall, 494 subjects were followed up for 346 ± 49 days and completed the study. Patients with good glycaemic control (HbA1c one-year mean < 7%) showed a higher virus-neutralizing antibody capacity and a better CD4 + T/cytokine response, compared with those with poor control (HbA1c one-year mean ≥ 7%). One-year mean of HbA1c was significantly associated with the incidence of breakthrough infections (adjusted hazard ratio [HR], 0.285; 95% confidence interval [CI], 0.106 to 0.768; p = 0.013). Among other factors, only smoking status was associated with the incidence of breakthrough infections (HR = 0.360, CI 0.181–0.716 for non-smokers). In summary, poor glycaemic control, assessed as mean HbA1c in the post-vaccination period, is associated with lower immune responses and an increased incidence of SARS-CoV-2 breakthrough infections in T2D patients vaccinated with mRNA-BNT162b2.