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Asthma and T1D in Kids: It's Complicated

— Why would an association go in only one direction?

MedpageToday
A young boy using a nebulizer at home

Children with asthma were more likely to have co-occurring type 1 diabetes, but the reverse was not true, according to a Swedish registry study.

Among more than one million children, those with asthma had a small but significant increased risk of being subsequently diagnosed with type 1 diabetes compared with children who did not have asthma (hazard ratio 1.17, 95% CI 1.07-1.28), reported Awad Smew, MD, of the Karolinska Institutet in Stockholm, Sweden, and colleagues.

However, children with type 1 diabetes versus those without did not have a greater risk of going on to develop asthma (HR 0.91, 95% CI 0.75-1.11), the team wrote in .

"Our findings could partially be explained by the fact that asthma in our sample occurred at a younger mean age than type 1 diabetes, meaning that children with both asthma and type 1 diabetes in general already had received their asthma diagnosis before they developed type 1 diabetes," Smew and co-authors wrote.

Prior research has suggested a but this idea was challenged by a 2003 meta-analysis that found a of asthma among kids with type 1 diabetes.

It may seem plausible that some factors, like early exposure to viruses, would play a role in the development of these two diseases, commented Michael Yafi, MD, of the McGovern Medical School at UTHealth in Houston, who was not involved with this research.

For example, early exposure to viruses is often associated with things like reactive airway disease and has also been shown to cause an autoimmune reaction, an indicator of type 1 diabetes, he explained.

"Many people are trying to understand the cause of type 1 diabetes, what is triggering this autoimmune reaction ... but I really don't think we can say it is a cause-and-effect relationship between asthma and type 1 diabetes," Yafi told app.

Missing from this analysis was whether children were on obesogenic steroid therapy for asthma, which could increase changes in body weight, said Benjamin Nwosu, MD, of the University of Massachusetts Medical School in Worcester, who was also not involved with this study.

Therefore, while these findings highlight the need for extra vigilance regarding hyperglycemia in children with asthma who are receiving standard therapy, they may be impacted by unmeasured confounders, Nwosu said.

"This missing piece could explain why the use of steroids, which increase body weight and suppress insulin actions, could easily lead to persistent hyperglycemia, or to the unmasking of latent type 1 or type 2 diabetes in children," Nwosu told app. "This is more of an iatrogenic effect than a molecular mechanistic phenomenon."

The study involved children born in Sweden from 2001 to 2013, identified as having asthma or type 1 diabetes through diagnoses and prescriptions listed in national registries.

In total, 1,284,748 children -- 51.4% male -- were included in the sample, of which 121,809 (9.5%) were diagnosed with asthma; 3,812 (0.3%) were diagnosed with type 1 diabetes; and 494 (0.04%) were diagnosed with both.

Children with asthma were diagnosed at a mean age of 3, whereas children with type 1 diabetes were diagnosed at a mean age of 5.9, the authors reported.

To examine the familial coaggregation of both conditions, researchers also identified 835,412 siblings, of whom 9.6% had asthma, 0.3% had type 1 diabetes, and 0.04% had both.

Siblings of individuals with either type 1 diabetes or asthma were also significantly more likely to be diagnosed with the other disease (odds ratio 1.27, 95% CI 1.13-1.42), as were cousins (OR 0.72, 95% CI 0.45-1.16), the researchers reported. Half-siblings showed no such association, the team added.

However, these familial associations are limited by the lack of assessment of shared genetic factors, "making the findings in siblings rather tenuous," Nwosu said.

Additional limitations include the exclusion of diagnoses from primary care physicians and a lack of power to detect differences in risk between half-family members, the authors noted, adding that they also restricted the sample to children diagnosed with type 1 diabetes after age 1, missing neonatal diabetes diagnoses. Parental patterns of disease were also missing.

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    Elizabeth Hlavinka covers clinical news, features, and investigative pieces for app. She also produces episodes for the Anamnesis podcast.

Disclosures

The study was funded by the Swedish Research Council, the Swedish Initiative for Research on Microdata in the Social and Medical Sciences, the Stockholm County Council, and the Swedish Heart-Lung Foundation.

Smew and co-authors did not report any relevant disclosures.

Primary Source

JAMA Network Open

Smew A, et al "Familial coaggregation of asthma and Type 1 diabetes in children" JAMA Netw Open 2020; 3(3): e200834.