Insulin Resistance Linked to Lung Abnormalities and Disease Risk: Insights From Framingham Study

The research published in Diabetes Care found that insulin resistance is associated with radiographic lung abnormalities and an increased risk of incident lung disease. These findings suggest a potential link between metabolic dysfunction and lung health, emphasizing the need for deeper phenotyping to understand better the mechanisms driving IR-associated lung injury.

Insulin resistance has been suggested as a potential risk factor for lung disease, though objective evidence remains limited. To address this gap, Tianshi David Wu, Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX, and colleagues investigated the relationship between longitudinal IR levels, radiographic imaging findings, and examiner-confirmed incident lung disease within the Framingham Offspring Study cohort.

For this purpose, the researchers analyzed data from participants without baseline lung disease, who underwent repeated measurements of fasting insulin and glucose levels over an average of 13.6 years. From these measurements, time-weighted average HOMA-IR values were calculated. Each participant then received a cardiac-gated whole-lung computed tomography (CT) scan, which was evaluated for emphysema, interstitial lung abnormalities (ILAs), and quantitative airway features.

A study examiner identified incident lung disease. To estimate the relationship between HOMA-IR and these outcomes, researchers used models adjusted for factors such as demographics, BMI, and lifetime smoking history.

The following were the key findings of the study:

• Researchers analyzed data from 875 participants with longitudinal IR data and outcomes.
• The participants had a mean age of 51.5 years and an average BMI of 26.7 kg/m².
• HOMA-IR values showed temporal instability, with a within-person standard deviation (SD) of approximately two-thirds of the between-person SD.
• In adjusted models, a 1 SD increase in log(HOMA-IR) z score was linked to higher odds of qualitative emphysema (odds ratio [OR] 1.33).
• The same increase was associated with higher odds of interstitial lung abnormalities (ILAs) (OR 1.35).
• Modest increases in airway wall thickness and wall area percentage were also observed with higher HOMA-IR levels.
• A positive association between HOMA-IR and the incidence of lung disease supported these radiographic findings.

The findings also stress the broader implications of managing insulin resistance. Early detection and intervention could not only improve metabolic outcomes but also potentially reduce the risk of lung disease. As rates of metabolic disorders continue to climb, these insights could guide strategies to improve systemic and lung health.

"The Framingham Offspring Study sheds light on a previously underexplored link between insulin resistance and lung disease. The evidence underscores the importance of continued research to uncover the mechanisms of IR-associated lung injury and develop targeted interventions to mitigate its impact on respiratory health," the researchers concluded.

Reference: Sarath Raju, Paula Sierra, Vickram Tejwani, Kristen A. Staggers, Meredith McCormack, Dennis T. Villareal, Ivan O. Rosas, Nicola A. Hanania, Tianshi David Wu; Association of Insulin Resistance With Radiographic Lung Abnormalities and Incident Lung Disease: The Framingham Offspring Study. Diabetes Care 2024; dc241754. https://doi.org/10.2337/dc24-1754