Lung function declines more rapidly with greater severity of the disease in patients with asthma and co-existing insulin resistance, according to a study published in the American Journal of Respiratory and Critical Care Medicine.¹

A team of researchers from the United States examined 307 patients, aged 52 years (median), with severe asthma to explore the association between insulin resistance and pulmonary function including response to steroids and bronchodilators (β-adrenergic agonists). These patients were a part of the Severe Asthma Research Program 3 (SARP-3) study. Homeostatic model measure of insulin resistance (HOMA-IR) was used to assess insulin resistance (IR). Almost half (46%) of the patients had IR, of which 63 had moderate IR and 77 had severe IR. More than half (55%) of the participants were obese. FEV1 and FVC were measured pre- and post-treatment as well as annually for a duration of 5 years.

Although BMI correlated significantly with IR, 11% of patients had IR but were not obese, while  21% of patients had obesity but did not have IR.

A substantial reduction in both pre-and post-bronchodilator FEV1 and FVC values was observed in patients with insulin resistance than in those without IR.

The pre-bronchodilator FEV1 was 70.9% in patients with moderate IR, 68.3% in those with severe IR compared to 76.4% in those who did not have IR. The pre-bronchodilator FVC was 81.5% in patients with moderate IR, 78.3% in severe IR compared to 88.3% in patients who did not have IR. The post-bronchodilator values for FEV1 and FVC were 80.7% and 89.5%, respectively in those with moderate IR, 76.1% and 83.9%, respectively in those with severe IR compared to 86.1% and 94.8%, respectively in those without IR.

The annual decline of FEV1 was greater among asthmatic patients with IR versus those without -40 ml/year in patients with moderate IR, -32 ml/year in those with severe IR and -13 ml/year among those without IR. A similar trend was noted for FVC –43 mL/year in moderate IR vs –34 mL/year in severe IR vs–17 mL/year in without IR.

Bronchial asthma is more severe with frequent exacerbations and also less amenable to treatment in the obese patient.

This study has tried to find an answer to this conundrum. Majority of patients with asthma in this study were obese and most of them had insulin resistance. Patients with insulin resistance had poorly controlled asthma with less than optimal response to treatment with beta-agonists and oral steroids. They also exhibited greater and more rapid deterioration in pulmonary function compared to those who did not have insulin resistance. Hence, insulin resistance is a likely, but modifiable, risk factor for adverse lung function, the correction of which may improve control of severe asthma, especially in the obese patient. Further studies may shed more light on causative associations between asthma, IR and obesity.

Reference

1. Peters  MC, et al; National Heart, Lung, and Blood Institute Severe Asthma Research Program-3. The impact of insulin resistance on loss of lung function and response to treatment in asthma. Am J Respir Crit Care Med. 2022 Nov 1;206(9):1096-1106. doi: 10.1164/rccm.202112-2745OC.