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. 2018 Sep;61(9):1996-2004.
doi: 10.1007/s00125-018-4662-7. Epub 2018 Jun 22.

Pandemic Influenza and Subsequent Risk of Type 1 Diabetes: A Nationwide Cohort Study

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Free PMC article

Pandemic Influenza and Subsequent Risk of Type 1 Diabetes: A Nationwide Cohort Study

Paz L D Ruiz et al. Diabetologia. .
Free PMC article

Abstract

Aims/hypothesis: Case 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.

Methods: In 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 2006-2014 (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.

Results: The 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/interpretation: Overall, 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).

Keywords: Incidence; Infections; Influenza; Influenza H1N1; Register-based study; Type 1 diabetes.

Conflict of interest statement

HLG has received grants for lectures or consulting from AstraZeneca, Novo Nordisk, Sanofi, Boehringer Ingelheim and Merck Sharp & Dohme. All other authors declare that there is no duality of interest associated with their contribution to this manuscript.

Figures

Fig. 1
Fig. 1
Overview of nationwide registers linked via personal identification numbers assigned to all Norwegian residents. Laboratory-confirmed influenza data are from the MSIS register, May 2009 to April 2011. The Norwegian Patient Registry collects data on individuals receiving specialist healthcare (inpatient and outpatient) (see ESM Table 1 for codes and abbreviations). SYSVAK is a national electronic immunisation registry that records an individual’s vaccination status and vaccination coverage in Norway (ICD-10, ICPC-2, the Anatomical Therapeutic Chemical). Blue brackets represent the seasonal influenza period each year (for 2006, data were available from 1 January). ATC, Anatomical Therapeutic Chemical; Jan, January; Jun, June
Fig. 2
Fig. 2
Association between pandemic influenza diagnosis and risk of type 1 diabetes in up to 2.28 million Norwegian residents under 30 years of age, overall and in subgroups. Incident cases of type 1 diabetes defined as registration of dispensed insulin for at least 6 months and at least one registration of a type 1 diabetes diagnosis from specialist or primary care. Pandemic influenza was defined as a clinical diagnosis of influenza registered in the primary care database, specialist care, or a laboratory-confirmed pandemic influenza (during the pandemic period). HRs were adjusted for year of birth, sex, place of birth, education and pandemic influenza vaccination (except analysis stratified for sex, which was adjusted for year of birth, place of birth, education and pandemic influenza vaccination). Exp., exposed; Lab, laboratory; T1D, type 1 diabetes; Unexp., unexposed
Fig. 3
Fig. 3
Cumulative incidence and 95% CI of type 1 diabetes for pandemic influenza (blue line and grey shaded area) and for no pandemic influenza (red line and light red shaded area). Logrank test p = 0.049
Fig. 4
Fig. 4
Association between seasonal influenza diagnosis and risk of type 1 diabetes in more than 2.5 million individuals under 30 years of age (a), and under 15 years of age (b). HRs were adjusted for year of birth, sex, place of birth and education. Seasonal influenza from 1 January 2006 to 30 June 2014 (the pandemic season, 2009–2010, shows the same data as in Fig. 2; during this season, pandemic influenza was defined as an influenza registration in primary care or in specialist care or laboratory-confirmed pandemic influenza). Exp., exposed; Unexp., unexposed

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