Insulin resistance linked to poorer asthma outcomes

Patients with asthma and insulin resistance had lower and faster loss of lung function, as well as suboptimal responses to asthma treatments, according to a study published in American Journal of Respiratory and Critical Care Medicine.

“The effect of insulin resistance on disease severity and lung function in asthma is poorly understood, and the effect of IR [insulin resistance] on changes in lung function over time has not been studied to our knowledge,” Michael C. Peters, MD, assistant professor of medicine in the division of pulmonary and critical care medicine and the department of medicine at the University of California, San Francisco, and colleagues wrote. “In addition, the effect of IR on lung function responses to beta-adrenergic agonists or corticosteroids has not been reported.”

Peters and colleagues analyzed 307 adults with severe asthma from the Severe Asthma Research Program 3 (SARP-3) study to find out whether IR was related to lung function impairments and treatment responses to bronchodilators and corticosteroids.

To evaluate IR, researchers used a homeostatic model measure of insulin resistance (HOMA-IR) and grouped these values into one of three categories to demonstrate varying levels of IR severity: without (< 3), moderate (3-5) and severe (> 5).

Of the total cohort, researchers found that 170 (55%) patients had obesity according to WHO’s definition, and 140 (46%) patients had IR, including 63 patients with moderate IR and 77 with severe IR. Median age of participants was 52 years across IR groups, with a majority being women (61%-75%).

Researchers noted that BMI was significantly associated with HOMA-IR (P < .001), but 21% of patients had obesity without IR, and 11% had IR without obesity.

Researchers assessed lung function using measurements of FEV₁ and FVC, taken both before and after receiving inhaled albuterol and intramuscular triamcinolone acetonide treatments, as well as every year for 5 years.

Results showed lower values of lung function among patients pre-bronchodilator with moderate IR (FEV₁ = 70.9%; FVC = 81.5%) and severe IR (FEV₁ = 68.3%; FVC = 78.3%) compared with those without IR (FEV₁ = 76.4%; FVC = 88.3%). Similar results were found post-bronchodilator (without IR, FEV₁ = 86.1%; FVC = 94.8% vs. moderate IR, FEV₁ = 80.7%; FVC = 89.5% vs. severe IR, FEV₁ = 76.1%; FVC = 83.9%).

According to researchers, obesity could not be attributed to the observed lower lung function values according to linear regression analyses controlled for BMI as well as analyses of HOMA-IR and lung function restricted to patients with morbid obesity.

Next, researchers assessed associations between IR and response to treatment with up to 720 µg albuterol using the maximum bronchodilator reversibility test, and with a 40 mg intramuscular injection of triamcinolone acetonide using systemic corticosteroid response test.

During baseline and 3-year visits, patients with severe IR had significantly lower FEV₁ responses to albuterol. Similarly, researchers found a significantly lower FEV₁ response to systemic triamcinolone acetonide at baseline in patients with moderate or severe IR compared with those without IR.

Additionally, results of a multilevel mixed effects linear regression model showed larger yearly declines of FEV₁ among patients with vs. without IR (without, –13 mL/year; vs. moderate, –40 mL/year; P < .001; vs. severe, –32 mL/year; P = .001), with similar findings for FVC (without IR, –17 mL/year vs. moderate IR, –43 mL/year; P < .001; vs. severe IR, –34 mL/year; P = .02).

According to researchers, the faster loss of lung function present in those with moderate and severe IR also surpassed what was expected when considering normal lung aging.

“These results provide rationale to consider clinical trials that test whether treatments for insulin resistance prevent accelerated loss of lung function in asthma,” Peters and colleagues wrote.

This study by Peters and colleagues adds to the literature indicating that the association between IR and lung function loss needs to be studied further to understand causation, according to an accompanying editorial by James P. Allinson, MD, PhD, of the National Heart and Lung Institute at Imperial College London and the Royal Brompton Hospital in London, and colleagues.

“As the authors infer, IR could be driving lung function loss, but it is also possible that this association instead reflects the clustering of susceptibility factors in the same individuals,” Allinson and colleagues wrote. “Exposures we encounter across our whole life course, and even prenatally, help shape our respiratory and metabolic health in adulthood.

“Notwithstanding the caveats regarding assuming causality, this study provides a stimulating argument for further scrutiny of the coexistence of asthma, IR, and obesity to ensure that we are managing affected individuals as effectively as possible,” Allinson and colleagues added. “Further population studies, analysis of data sets from prior diabetic drug studies or new randomized control trials of IR targeting therapies may provide support for the reported relationships and indicate whether there is potential for intervention.”

Reference:

Allinson JP, et al. Am J Respir Crit Care Med. 2022;doi:10.1164/rccm.202207-1271ED.