Baylor College of Medicine researchers in Waco, Texas, have shed light on the role high blood sugar may play in a previously underrecognized worsening lung function for adults with asthma. The findings point to hyperglycemia — rather than insulin resistance alone — as a potential driver of small airways dysfunction, a condition that can be difficult to detect with standard lung tests. Their paper, “Hyperglycemia, Receptor for Advanced Glycation End Products and Small Airways Dysfunction in Asthma,” was published in the Annals of Allergy, Asthma & Immunology.
Researchers followed 65 adults with physician-diagnosed asthma, measuring their glucose levels, hemoglobin A1c, insulin resistance, lung function and levels of 13 blood proteins associated with diabetes-related organ damage. Participants were evaluated using both traditional spirometry and oscillometry, a more sensitive tool capable of detecting subtle changes in the small airways.
Among participants not taking medications for diabetes, hypertension or dyslipidemia, elevated blood sugar and A1c levels were strongly associated with signs of small airways dysfunction (SAD). Oscillometry revealed increased airway resistance and greater abnormalities in airway reactance — markers that suggest stiffening, narrowing or inflammation within the small airways.
According to researchers, these abnormalities were also linked to a higher likelihood of presenting with a Preserved Ratio Impaired Spirometry (PRISm) pattern, where lung function is reduced but the ratio of key airflow measurements remains normal. The paper’s authors said this pattern has puzzled researchers for years because it often does not resemble classic asthma obstruction.
The study also identified a promising biomarker: soluble receptor for advanced glycation end products (sRAGE). Researchers noted that participants with higher sRAGE levels showed lower inflammation, lower A1c values and better lung function.
The receptor is known to protect against diabetes-related organ damage and regulates inflammatory responses in the lungs. The paper’s authors suggested sRAGE may help explain how hyperglycemia affects airway inflammation and structure.
Previous epidemiologic studies have shown that patients with type 2 diabetes or insulin resistance are at greater risk of asthma exacerbations, the authors noted, but the mechanisms behind this link have been unclear. Preclinical studies have shown that elevated glucose and insulin can thicken airway walls, increase collagen deposition and promote inflammation — changes that mirror those seen in chronic asthma, they said.
Of additional note, the associations disappeared among participants taking metabolic medications such as metformin or statins, implying that these drugs may offer some protection to lung function.
Researchers cautioned that the study is observational and based on a single evaluation, meaning it cannot prove causation, and said larger longitudinal studies will be needed to determine whether better glucose control can help prevent or reverse small airways dysfunction in asthma.
Ultimately, they noted that the findings highlight a potentially important — and modifiable — risk factor for millions of adults with asthma.
