Abstract
Aims/hypothesisCase reports have linked influenza infections to the development of type 1 diabetes. We investigated whether pandemic and seasonal influenza infections were associated with subsequent increased risk of type 1 diabetes.MethodsIn this population-based registry study, we linked individual-level data from national health registries for the entire Norwegian population under the age of 30 years for the years 2006â2014 (2.5 million individuals). Data were obtained from the National Registry (population data), the Norwegian Patient Registry (data on inpatient and outpatient specialist care), the Primary Care Database, the Norwegian Prescription Database and the Norwegian Surveillance System for Communicable Diseases. Pandemic influenza was defined as either a clinical influenza diagnosis during the main pandemic period or a laboratory-confirmed test. Seasonal influenza was defined by a clinical diagnosis of influenza between 2006 and 2014. We used Cox regression to estimate HRs for new-onset type 1 diabetes after an influenza infection, adjusted for year of birth, sex, place of birth and education.ResultsThe adjusted HR for type 1 diabetes after pandemic influenza infection was 1.19 (95% CI 0.97, 1.46). In the subgroup with laboratory-confirmed influenza A (H1N1), influenza was associated with a twofold higher risk of subsequent type 1 diabetes before age 30 years (adjusted HR: 2.26, 95% CI 1.51, 3.38).Conclusions/interpretationOverall, we could not demonstrate a clear association between clinically reported pandemic influenza infection and incident type 1 diabetes. However, we found a twofold excess of incident diabetes in the subgroup with laboratory-confirmed pandemic influenza A (H1N1).
Highlights
Type 1 diabetes is a chronic autoimmune disease with both genetic and environmental contributions
New-onset type 1 diabetes was registered at a slightly younger age for those registered with pandemic influenza diagnosis compared with those without such registration (12.9 years compared with 13.3 years)
In the analysis of those with pandemic influenza diagnosed in specialist healthcare, the adjusted HR was 2.83, 95% CI 1.18, 6.81 (Fig. 2; of those, four of five new cases of type 1 diabetes were laboratory confirmed)
Summary
Type 1 diabetes is a chronic autoimmune disease with both genetic and environmental contributions. Viruses may influence susceptibility and trigger autoimmunity in individuals genetically predisposed to diabetes [1, 2]. Enteroviruses and other viruses have been most frequently studied in relation to type 1 diabetes [3]. Respiratory virus infections have been associated with the development of islet autoimmunity and the first manifestations of clinical symptoms of type 1 diabetes [4,5,6,7,8]. Influenza A (H1N1) virus infection has been associated with acute pancreatitis [10,11,12] and type 1 diabetes [13, 14] in human case-report studies
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