Bacterial infections as novel risk factors of severe diabetic retinopathy in individuals with type 1 diabetes

Abstract

Background/Aims Diabetic retinopathy (DR) is associated and shares many risk factors with other diabetic complications, including inflammation. Bacterial infections, potent inducers of inflammation have been associated with the development of diabetic complications apart from DR. Our aim was to investigate the association between bacterial infections and DR. Methods Adult individuals with type 1 diabetes (n=1043) were recruited from the Finnish Diabetic Nephropathy Study (FinnDiane), a prospective follow-up study. DR was defined as incident severe diabetic retinopathy (SDR), identified as first laser treatment. Data on DR were obtained through fundus photographs and medical records, data on bacterial infections from comprehensive national registries (1 January 1995 to 31 December 2015). Risk factors for DR and serum bacterial lipopolysaccharide (LPS) activity were determined at baseline. Results Individuals with incident SDR (n=413) had a higher mean number of antibiotic purchases/follow-up year compared with individuals without incident SDR (n=630) (0.92 [95% CI 0.82 to 1.02] vs 0.67 [0.62-0.73], p=0.02), as well as higher levels of LPS activity (0.61 [0.58-0.65] vs 0.56 [0.54-0.59] EU/mL, p=0.03). Individuals with on average ≥1 purchase per follow-up year (n=269) had 1.5 times higher cumulative incidence of SDR, compared with individuals with <1 purchase (n=774) per follow-up year (52% vs 35%, p<0.001). In multivariable Cox survival models, the mean number of antibiotic purchases per follow-up year as well as LPS activity were risk factors for SDR after adjusting for static confounders (HR 1.16 [1.05-1.27], p=0.002 and HR 2.77 [1.92-3.99], p<0.001, respectively). Conclusion Bacterial infections are associated with an increased risk of incident SDR in type 1 diabetes.