Use of Antiasthmatic Drugs and the Risk of Type 1 Diabetes in Children

A Nationwide Case-Cohort Study

Johanna Metsälä; Annamari Lundqvist; Lauri J. Virta; Minna Kaila; Mika Gissler; Suvi M. Virtanen; Jaakko Nevalainen


Am J Epidemiol. 2020;189(8):779-787. 

In This Article

Abstract and Introduction


Asthma has been reported to be associated with an increased risk of type 1 diabetes mellitus in childhood, but the reasons are unclear. We examined whether the use of antiasthmatic drugs was associated with the development of type 1 diabetes in childhood in a nationwide, register-based case-cohort study. We identified all children who were born January 1, 1995, through December 31, 2008, in Finland and diagnosed with type 1 diabetes by 2010 (n = 3,342). A 10% random sample from each birth-year cohort was selected as a reference cohort (n = 80,909). Information on all dispensed antiasthmatic drugs (Anatomical Therapeutic Chemical classification system code R03) during 1995–2009 was obtained, and associations between the use of antiasthmatic drugs and the development of type 1 diabetes were investigated using time-dependent and time-sequential Cox regression models. Dispensed inhaled corticosteroids and inhaled β-agonists were associated with an increased risk of type 1 diabetes after adjusting for other antiasthmatic drugs, asthma, sex, and birth decade (hazard ratio = 1.29, 95% confidence interval: 1.09, 1.52, and hazard ratio = 1.22, 95% confidence interval: 1.07, 1.41, respectively). These findings suggest that children using inhaled corticosteroids or inhaled β-agonists might be at increased risk of type 1 diabetes.


The association between asthma and type 1 diabetes mellitus, 2 different types of immune-mediated diseases, has been investigated in several studies with both increased and decreased risks reported.[1–5] We have recently reported that prior asthma increases the risk of subsequent type 1 diabetes by 41% compared with children without asthma.[6] Whether the association between asthma and type 1 diabetes in children is related to asthma as a disease itself, the treatment of asthma, or some other yet unknown factor has not been investigated previously.

Inhaled corticosteroids (ICS) are a cornerstone of asthma treatment, but despite their evident advantages in managing airway inflammation and asthma symptoms, concern about adverse systemic effects remains.[7] A recent systematic review on the adverse effects of antiasthmatic drugs in children reported that the majority of the existing data focused on ICS, and mainly adrenaline and growth suppression were described.[8] Evidence on ICS associations with glycemic or diabetic outcomes stems mainly from adult populations: ICS-induced hyperglycemia has been observed among individuals with preexisting diabetes, but an increased risk of new-onset type 2 diabetes has also been observed in some although not all studies.[9] β-agonists, another common drug group used in asthma treatment, might also affect glucose homeostasis, but the clinical relevance of these findings is uncertain.[10] Thus, evidence for whether antiasthmatic drugs are associated with glycemic outcomes in children is limited, and it is lacking in relation to the development of diabetes.

The aim of the present study was to examine whether antiasthmatic drug use is associated with the risk of type 1 diabetes in childhood. We hypothesized that the use of antiasthmatic drugs is associated with an increased risk of type 1 diabetes and thus might explain our previous finding of prior asthma increasing the risk of subsequent development of type 1 diabetes.