Influenza Vaccination Among Individuals With Type 1 Diabetes in Denmark: Coverage, Persistence, and Determinants, 2015–2022

ABSTRACT

Aims

To investigate influenza vaccination coverage (IVC) and persistence with annual influenza vaccination among individuals with type 1 diabetes in Denmark and to identify clinical, demographic, and socioeconomic factors associated with vaccination status.

Materials and Methods

We conducted a nationwide, register‐based cohort study of individuals aged 1–64 years with type 1 diabetes across the influenza seasons 2015–2022 in Denmark. Annual influenza vaccination status was assessed, and the cohort was stratified into age groups (1–18 and 19–64 years) according to age‐specific vaccine recommendations. We investigated associations between non‐vaccination/non‐persistence and demographic, clinical, and socioeconomic factors using Poisson regression to compute adjusted relative risk (aRR). Persistence was defined as receipt of influenza vaccination in more than 80% of eligible seasons during follow‐up.

Results

We identified 25 473 individuals with type 1 diabetes corresponding to 168 212 influenza seasons. In 2015/16, IVC was 5.6% in children and 18.3% in adults. IVC remained stable until a marked increase in 2021/22 (15.7% and 41.8%, respectively). In children, longer diabetes duration, HbA1c ≥ 53 mmol/mol, and residence in The North Denmark Region were associated with non‐vaccination. In adults, male sex, younger age, shorter educational attainment, and HbA1c ≥ 53 mmol/mol were associated with non‐vaccination. In both populations, factors associated with non‐persistence were similar to those observed with non‐vaccination.

Conclusions

In Denmark, IVC among individuals with type 1 diabetes remains well below WHO targets, highlighting the need for targeted vaccination strategies. Sociodemographic and clinical factors associated with non‐vaccination identify population groups where preventive efforts should be prioritised.

1. Introduction

Influenza is a common viral infection with variable incidence and severity, ranging from milder upper respiratory tract illness to severe lower respiratory tract complications requiring hospitalisation or intensive care, and in some cases resulting in death. Influenza infection is preventable by vaccination, making higher annual vaccination coverage in at‐risk groups essential [1, 2].

Influenza infection triggers stress hormone responses and proinflammatory cytokine release, inducing insulin resistance [3]. Infection also increases dehydration risk and alters diet and physical activity, contributing to dysregulated glycaemic control [3, 4]. Insufficient glycaemic control increases the risk of severe infection [4]. Therefore, individuals with type 1 diabetes (T1D) are at higher risk of complications, including ketoacidosis, hospitalisation, intensive care admission, and death [5].

In Denmark, influenza vaccination is provided free of charge to all individuals with T1D during the influenza season (October 1 to March 1) [6]. The Danish Health Authorities recommend annual influenza vaccination to all individuals with T1D, while the current national guideline from The Danish Paediatric Society targets a narrower group, recommending vaccination only for children and adolescents with insufficient glycaemic control [6, 7, 8]. The World Health Organisation (WHO) and the European Commission have set a target influenza vaccination coverage (IVC) of 75% for at‐risk groups, including T1D [9]. A European Centre for Disease Prevention and Control report (2024), based on data from four EU/EEA countries, reported IVC ranging from 25.8% to 77% among individuals with chronic medical conditions, without specification of the underlying conditions [10].

IVC and its determinants among individuals with T1D remain poorly investigated [11, 12]. This register‐based study aims to assess IVC, persistence across multiple seasons, and factors associated with non‐vaccination among Danish individuals with T1D.

2. Materials and Methods

Denmark maintains comprehensive nationwide health registries covering the entire population (≈6 million in 2025) [13]. The Danish national health registers are unique, using a mandatory personal identification number and compulsory vaccine registration providing population‐wide coverage, capturing all eligible individuals regardless of age, sex, or socioeconomic status [13]. The registers minimise selection bias in register‐based studies and allow comprehensive longitudinal assessment of vaccination behaviour among all individuals with T1D in Denmark. We extracted data from these registries and linked records using this identifier, assigned to all Danish citizens at birth or immigration.

2.1. Data Sources

All data used in this study were obtained exclusively from Danish registries. The covariates included sex, age, T1D duration, region of residence, haemoglobin A1c (HbA1c), years of education, employment status, events of hypoglycaemia and ketoacidosis, and influenza vaccination status in the previous season. Time‐dependent variables were reassessed at the start of each season.

Date of diabetes diagnosis was obtained using the Open‐Source Diabetes Classifier, a previously validated algorithm, which defines diabetes status using a combination of HbA1c measurements, hospital diagnosis of T1D, diabetes‐specific visits at the podiatrist, and purchases of glucose lowering drugs [14].

Vaccination status for each influenza season, as well as the previous season, was obtained from The Danish Vaccination Registry. Information on sex, date of birth, and region of residence (Capital Region of Denmark/Central Denmark Region/North Denmark Region/Region Zealand/Region of Southern Denmark) was retrieved from the Danish Civil Registration System [15].

The latest HbA1c measurement before each season was obtained from the Register of Laboratory Results for Research [16].

Information on hospital admissions due to severe hypoglycaemia and ketoacidosis prior to each season was retrieved from The Danish National Patient Registry [17]. Relevant ICD‐10 diagnosis codes are listed in Table S1.

The highest attained education level was assessed using the Attainment Register [18]. Employment status was extracted from the Employment Classification Module [19].

2.2. Study Population and Follow‐Up

This study included the entire nationwide population of individuals with T1D meeting eligibility criteria, with no a priori sample size calculation. We compiled a cohort of all Danish citizens diagnosed with T1D, aged 1–64 years and residing in Denmark from October 1st, 2015, to July 1st, 2022. Influenza seasons from 2015/16 to 2022/23 were included, each defined as the period from October 1st to September 30th of the following year to capture vaccination timing and follow‐up. Individuals who met the inclusion criteria contributed a person‐year (PY) for each season they were included.

To be included in the influenza season of a given year, individuals had to be alive and reside in Denmark with a diagnosis of T1D on or before October 1st of that year. Individuals were stratified into two age groups based on age at season start to account for age‐specific influenza vaccination recommendations: 1–18 years (paediatric population) and 19–64 years (adult population).

In Denmark, all individuals > 65 years of age are eligible for free influenza vaccination regardless of chronic conditions [20] and were therefore excluded to minimise confounding from overlapping vaccination incentives.

To ensure availability of vaccination data from the previous season and to avoid bias related to timing of diagnosis, we excluded individuals diagnosed with T1D between October 1, 2014, and September 30, 2015, as well as each individual's first season after diagnosis from October 1, 2015, onward. Flowchart of the cohort selection process is shown in Figure S1.

2.3. Outcome

IVC was calculated each season as vaccines administered divided by population size and reported with 95% confidence intervals (95% CI). Persistence was defined as receipt of influenza vaccination in > 80% of seasons. The > 80% threshold was chosen to reflect frequent or repeated vaccination behaviour, consistent with a previous study that defined individuals vaccinated in 4–5 of 5 seasons (80%–100%) as ‘Frequent vaccinees’ [21].

2.4. Statistical Analysis

Factors associated with IVC and persistence were analysed in age‐specific groups using Poisson regression with robust standard errors. To account for individuals eligible in several influenza seasons contributing multiple observations, all regression analyses were clustered at the individual level. Associations are reported as adjusted relative risks (aRRs) with 95% confidence intervals (CI). We adjusted for all variables mutually.

Covariates were defined as follows: Age and diabetes duration were defined at the start of each season and modelled as categorical variables using quartiles. HbA1c was categorised as either above or in target that is, HbA1c < 53 mmol/mol, in accordance with the Danish Endocrine Society's treatment goal for individuals with T1D [10]. For severe hypoglycaemia and ketoacidosis, individuals who had experienced at least one hospital admission for either condition prior to the start of each season were coded as ‘Yes’. Education level was categorised as years of education in intervals: 0–10 years, 11–15 years and > 15 years. Employment was categorised as employed (including students), retired or unemployed.

Missing values were imputed using the last observation carried forward (LOCF) method in R. LOCF was chosen because several variables included in the analyses were expected to remain relatively stable across influenza seasons, including HbA1c, employment status, and education level.

LOCF was considered appropriate due to the longitudinal structure of the dataset, repeated annual measurements and the limited proportion of missing observations requiring imputation. Overall, 13.1% of HbA1c values, 12.6% of employment observations and 0.09% of education observations were imputed using LOCF. Observations with remaining missing values after LOCF were excluded from analyses (Figure S2).

Data management and statistical analyses were performed using R version 4.3 and packages from the Comprehensive R Archive Network.

3. Results

We included 25 473 individuals with T1D contributing 168 212 person‐years of follow‐up. Distributions of cohort characteristics for each age group are found in Table 1. Across both age groups, individuals contributed a median of 8 seasons.

TABLE 1.

Characteristics of a total 168 212 person‐years (25 473 individuals with type 1 diabetes) stratified by age groups.

	Person‐years aged 1–18, n = 16 642		Person‐years aged 19–64, n = 151 570
	Vaccinated n = 1411 (8.5%)	Non‐vaccinated n = 15 231 (91.5%)	Vaccinated n = 42 210 (27.8%)	Non‐vaccinated n = 109 360 (72.2%)
Demographic and socioeconomic characteristics
Male sex	729 (51.7)	7921 (52.0)	21 280 (50.4)	66 985 (61.3)
Seasons contributed per person	8.0 (5.0, 8.0)	8.0 (6.0, 8.0)	8.0 (8.0, 8.0)	8.0 (8.0, 8.0)
Region
Capital Region of Denmark	472 (33.5)	4979 (32.7)	11 531 (27.3)	31 910 (29.2)
Central Region of Denmark	413 (29.3)	3864 (25.4)	10 601 (25.1)	25 313 (23.1)
North Region of Denmark	75 (5.3)	1299 (8.5)	4503 (10.7)	12 324 (11.3)
Region Zealand	170 (12.0)	1926 (12.6)	5374 (12.7)	15 619 (14.3)
Southern Region of Denmark	281 (19.9)	3163 (20.8)	10 201 (24.2)	24 194 (22.1)
Employment status a
Employed	1295 (91.8)	14 231 (93.4)	27 589 (65.4)	83 471 (76.3)
Unemployed	108 (7.7)	978 (6.4)	13 762 (32.6)	24 956 (22.8)
Retired	8 (0.6)	22 (0.1)	859 (2.0)	933 (0.9)
Highest completed education in years b
0–10	29 (2.0)	435 (2.9)	3674 (8.7)	10 766 (9.8)
11–15	632 (44.8)	6969 (45.8)	25 722 (60.9)	69 698 (63.7)
> 15	750 (53.2)	7827 (51.4)	12 814 (30.4)	28 896 (26.4)
Clinical and diabetes‐related characteristics
Age at onset (years)	9.0 (5.0, 12.0)	8.0 (5.0, 11.0)	24.0 (15.0, 33.0)	21.0 (13.0, 31.0)
T1D duration at season start (years)	5.0 (2.0, 8.0)	5.0 (3.0, 8.0)	22.0 (13.0, 31.0)	17.0 (9.0, 25.0)
HbA1c above treatment target c	956 (67.8)	11 506 (75.5)	31 514 (74.7)	85 987 (78.6)
Severe hypoglycaemic event before season start	96 (6.8)	917 (6.0)	2955 (7.0)	6641 (6.07)
Ketoacidosis before season start	259 (18.4)	2612 (17.2)	2661 (6.3)	8406 (7.69)
Vaccination previous season	679 (48.1)	383 (2.5)	28 169 (66.7)	8185 (7.48)

Note: The distribution of study population characteristics was tabulated by age and vaccination status and reported as frequencies (%) or median (interquartile range).

Abbreviations: HbA1c, haemoglobin A1c; T1D, type 1 diabetes.

^a For those aged 1–18: Parents' highest employment status.

^b For those aged 1–18: Parents' highest completed education in years.

^c Treatment target according to Danish guidelines: < 53 mmol/mol for all individuals with type 1 diabetes [10].

3.1. Influenza Vaccination Coverage

In the paediatric population, IVC was 5.6% in season 2015/16 and remained stable through 2020/21, after which it increased markedly to 15.7% in 2021/22 and peaked at 16.9% in 2022/23 (Figure 1).

FIGURE 1.

Influenza vaccination coverage within age groups in percent shown separately for each season.

In the adult population, IVC increased from 18.3% in 2015/16 to 41.8% in 2022/23, with a gradual upward trend followed by a pronounced increase in 2021/22, after which IVC remained high in 2022/23 (Figure 1). Season‐specific IVC estimates are available in Table S3. In sensitivity analyses including only individuals aged ≥ 65 years, IVC was substantially higher compared to the adult and paediatric population, with IVC being 57.6% in 2015/16 and increasing to 81.2% in 2021/22 (Table S4).

3.2. Factors Associated With Vaccination in the Paediatric Population

Individuals aged 16–18 years were more likely to be vaccinated compared with younger age groups (aRR 1.18, 95% CI 1.04–1.33) (Figure 2). IVC declined with increasing diabetes duration, and insufficient glycaemic control (HbA1c ≥ 53 mmol/mol) was associated with lower coverage (aRR 0.87, 95% CI 0.79–0.95). Children and adolescents residing in the North Denmark Region had lower IVC compared to the Capital Region (aRR 0.80, 95% CI 0.65–0.98). Children and adolescents with retired parents had higher IVC (aRR 1.73, 95% CI 1.25–2.40). The factor most strongly associated with IVC was receiving a vaccination in the preceding season (aRR 16.68, 95% CI 15.17–18.35) (Figure 2).

FIGURE 2.

Forest plot of factors associated with influenza vaccination in paediatric population. Reported with adjusted relative risks and 95% confidence intervals. Adjusted for all variables mutually. Note the logarithmic x‐axis. Abbreviations: Ref., reference. T1D, type 1 diabetes. HbA1c, haemoglobin A1c. Capital, The Capital Region of Denmark. Central, Central Denmark Region. North, The North Denmark Region. Zealand, Region Zealand. South, The Region of Southern Denmark. aRR, adjusted relative risk. 95% CI, 95% confidence interval.

3.3. Factors Associated With Vaccination in the Adult Population

In the adult population, male sex was associated with lower IVC (aRR 0.90, 95% CI 0.90–0.91), while coverage increased with age (Figure 3). Insufficient glycaemic control (HbA1c ≥ 53 mmol/mol) was associated with lower IVC (aRR 0.95, 95% CI 0.94–0.96). Individuals residing in Region Zealand had slightly lower IVC compared to individuals residing in the Capital Region (aRR 0.97, 95% CI 0.95–0.99). Educational attainment of less than 15 years was associated with lower IVC, with the strongest association observed among individuals with 0–10 years of education (aRR 0.91, 95% CI 0.89–0.93) compared with education of 11–15 years (aRR 0.93, 95% CI 0.92–0.94). Higher IVC was observed among unemployed (aRR 1.06, 95% CI 1.05–1.07) and retired individuals (aRR 1.12, 95% CI 1.08–1.16). The factor most strongly associated with IVC was receiving a vaccination in the preceding season (aRR 7.90, 95% CI 7.75–8.05) (Figure 3). In Table S5, we present sensitivity analyses in which the adult cohort was extended to include individuals ≥ 65 years. In these analyses, the oldest age quartile [62–98 years] was strongly associated with increased IVC, while the previously observed positive association between retirement and IVC was attenuated. Table S6 additionally presents subgroup analyses restricted to individuals aged ≥ 65 years—no substantial associations were observed.

FIGURE 3.

Forest plot of factors associated with influenza vaccination in adult population. Reported with adjusted relative risks and 95% confidence intervals. Adjusted for all variables mutually. Note the logarithmic x‐axis.

3.4. Factors Associated With Influenza Vaccination Persistence

Analyses of vaccination persistence (IVC > 80% of eligible seasons) showed patterns similar to those observed for vaccination coverage. In the paediatric age group, low vaccination persistence was associated with insufficient glycaemic control and longer diabetes duration. Among adults, low persistence was associated with male sex and a previous episode of diabetic ketoacidosis, while higher persistence was associated with older age, unemployment and retirement. Detailed results are available in Tables S7 and S8. Sensitivity analyses using alternate thresholds (> 70% and > 85%) yielded largely similar estimates for both populations and did not materially alter our findings (Table S9 for paediatric and adult population estimates).

4. Discussion

In this nationwide Danish cohort study of individuals with T1D followed across eight influenza seasons, IVC remained below national and international recommendations. Although adult IVC increased in the 2021/22 season, uptake remained below the WHO target of 75%. Younger age, insufficient glycaemic control, region of residence, and shorter education were associated with non‐vaccination and non‐persistence, underscoring the need for more targeted initiatives.

Compared with our findings, considerably higher IVC has been reported in children with T1D in Spain, with coverage rates of 56.4% in the 2020/2021 season [22]. In contrast, lower coverage rates were reported in Crete for both children and adults with T1D (IVC 32.2% in 2020) [23]. A 2021 European report including individuals with chronic conditions—among whom T1D was included but not examined separately—across four EU/EEA countries (Norway, the Netherlands, Portugal, and France) reported IVC ranging from 25.8% to 77%, with a general increase following the COVID‐19 pandemic. A similar post‐pandemic increase was observed in our study and in a recent Spanish study [22].

The strongest predictor of higher IVC in both age groups was vaccination in the preceding season, consistent with multiple studies identifying prior vaccination as the most influential predictor of future uptake [24]. This highlights the importance of establishing early and sustained vaccination habits.

In Denmark, influenza vaccination is recommended for children with T1D, particularly in the presence of insufficient glycaemic control. Given these recommendations and the well‐established increased risk of influenza‐related complications among individuals with poorly controlled T1D [25], a higher vaccination coverage among children with insufficient glycaemic control could be expected. Despite this, we found that insufficient glycaemic control was associated with a lower likelihood of influenza vaccination in both paediatric and adult populations. This finding aligns with a prior study showing that each 1% increase in HbA1c level is associated with a 29% reduction in the likelihood of influenza vaccination [23], suggesting that individuals at highest clinical risk are less likely to receive vaccination. This emphasises the clinical importance of this gap in preventive care.

In both age groups, younger age was associated with non‐vaccination. Consistent with these findings, Diaz‐Garcia et al. reported increasing IVC with advancing age [22]. In the adult population, male sex was associated with non‐vaccination, in line with observations from a Spanish study [24]. In contrast, Rodríguez‐Rieiro et al. reported higher IVC among boys than girls in the paediatric population [24], whereas we observed no association between sex and IVC in children and adolescents.

Few studies have examined the relationship between socioeconomic status and IVC among individuals with T1D [22, 26]. In this study, associations between socioeconomic factors and IVC varied across age groups. In the adult population, shorter education was associated with lower IVC. In contrast, in the paediatric population, parental education was not associated with IVC, although significant regional differences were observed. Notably, the North Denmark Region (Northern Jutland) has lower average income and educational levels than the Capital Region [27], providing important socioeconomic context for the regional differences in IVC observed in our study. Another study, in children with T1D, found no association between socioeconomic status and IVC [22], while studies in children with at‐risk conditions, including a small subgroup with T1D, reported increased IVC among individuals with higher socioeconomic status [26]. Further research is needed to clarify the role of socioeconomic factors in vaccination uptake in this population.

Overall, our findings emphasise the need for increased focus on annual influenza vaccination among individuals with T1D, particularly among those with insufficient glycaemic control, adult men, children and adolescents. Targeted efforts, including education and greater involvement of healthcare providers, may be effective in improving the IVC and narrowing the gap between guideline recommendations and observed vaccination coverage [28]. Another factor likely contributing to the low IVC is that many healthcare providers perceive the risk and severity of influenza infection as low [29]. This perception could hypothetically lead to limited information being conveyed to individuals with T1D regarding influenza and the importance of participating in the vaccination programme. Increasing IVC among individuals with T1D and other chronic conditions will offer several benefits for both patients and society, including a reduced risk of influenza infection, improved disease outcomes in case of severe infection, fewer influenza‐attributable deaths, and substantial health‐economic benefits [30].

5. Strengths and Limitations

The use of Danish registers offers several strengths: no recall/non‐response bias, nationwide coverage of all individuals with T1D and high data accuracy. The Open‐Source Diabetes Classifier is based on a validated algorithm for adults with T1D [14], thereby reducing the risk of misclassification. Although the Danish Vaccination Registry has not been formally validated, reporting of administered vaccines has been mandatory since November 2015, and follow‐up in this study began on October 1, 2015. The Danish Vaccination Registry provides a calculated numerical value [1, 2, 3, 4, 5], “credibility indicator”, indicating who registered the vaccine (healthcare worker, citizen etc.). The credibility indicator reflects the reliability of the records, with higher values indicating greater credibility. Overall, 85% of credibility indicators were graded 4 or 5 (Table S10), indicating high validity of the registered influenza vaccines. Given this, we anticipate that the coverage, persistence, and associated estimates observed in this study accurately reflect vaccination patterns among Danish individuals with T1D.

A limitation of this study is that comorbidities and other potential motivators for vaccination were not included in the analyses. This may have led to an overestimation of coverage among individuals with T1D alone, as those with comorbid conditions may be more likely to be vaccinated because of more frequent interactions with the health care system. Another limitation is the lack of data on health care visits, which may influence vaccination opportunities. Additionally, we had no data on vaccination coverage or persistence to other vaccination programmes, such as COVID‐19 vaccination. This limits trend comparisons during the pandemic and prevents establishing an association between increased IVC and COVID‐19 vaccination. This study spans an exceptional period including the COVID‐19 pandemic; however, future IVC patterns in the post‐pandemic era remain uncertain. As an observational registry study, residual confounding from unmeasured factors such as health‐seeking behaviour or physician recommendations cannot be excluded. Misclassification of diabetes type is possible, particularly in younger individuals, and HbA1c values carried forward may not fully reflect glycaemic control. Requiring survival and residence at the start of each season may introduce survivorship bias and limit generalizability to newly diagnosed or older individuals. Although completeness in the Danish Vaccination Registry is high, some under‐registration of vaccinations, particularly those administered outside Denmark, may have resulted in minor misclassification. Finally, future research should investigate influenza‐related outcomes in relation to IVC patterns, as this would help clarify the clinical implications of the observed differences in coverage.

Funding

Data extraction from Statistics Denmark was funded by a research grant from Flu Lab.

Conflicts of Interest

V.K. received a funded research year salary from Steno Diabetes Center Aarhus (February 2024–January 2025). V.K., I.B.P., and A.A.I. are employed at Steno Diabetes Center Aarhus, which is partially funded by a non‐restricted grant from the Novo Nordisk Foundation. I.B.P. and K.K. received unrestricted research support from Flu Lab for influenza‐related research. I.B.P. received travel support from the Novo Nordisk Foundation. K.K. received institutional payments from Novo Nordisk and Novonesis and travel support from Sanofi. O.F. received consulting fees from GSK and honoraria from Pfizer and Sanofi Pasteur. E.T.V. reported advisory board participation with Sanofi‐Aventis and minor stock holdings in Novo Nordisk and Sanofi‐Aventis. A.H. and M.K. declares no conflicts of interest.

Supporting information

Data S1: International Classification of Diseases 10th revision diagnosis codes.

Figure S2: Cohort selection flowchart.

Table S3: Coverage and 95% confidence interval for each season.

Table S4: Coverage and 95% confidence interval for each season for subpopulation “Individuals > 65 years”.

Table S5: Factors associated with Influenza Vaccination Coverage (19–64 years + > 65 years).

Table S6: Factors associated with Influenza Vaccination Coverage (ONLY > 65 years).

Figure S7: Factors associated with influenza vaccination persistence (> 80%) in the pediatric population (1–18 years).

Figure S8: Factors associated with influenza vaccination persistence (> 80%) in the adult population (19–64 years).

Table S9: Sensitivity analyses of persistence (> 70% and > 85%) in both populations.

Table S10: Distribution of credibility indicator values for registered influenza vaccinations.

Karunakaran V., Pedersen I. B., Hjelholt A., et al., “Influenza Vaccination Among Individuals With Type 1 Diabetes in Denmark: Coverage, Persistence, and Determinants, 2015–2022,” Diabetes, Obesity and Metabolism 28, no. 9 (2026): 7923–7930, 10.1111/dom.70965.

Data Availability Statement

The data that support the findings of this study are available from Statistics Denmark. Restrictions apply to the availability of these data, which were used under licence for this study. Data are available from the authors with the permission of Statistics Denmark.