ASSOCIATION OF INSULIN RESISTANCE WITH RADIOGRAPHIC LUNG ABNORMALITIES AND INCIDENT LUNG DISEASE: THE FRAMINGHAM OFFSPRING STUDY

ObjectiveInsulin resistance (IR) may be a risk factor for lung disease, but objective evidence is limited. We sought to define the relationship of longitudinal IR to radiographic imaging outcomes and examiner-identified incident lung disease in the Framingham Offspring Study.

Research Design and Methods
Participants without baseline lung disease underwent repeated measurements of fasting insulin and glucose over an average period of 13.6 years, from which time-weighted average HOMA-IR (homeostatic model assessment of insulin resistance) was calculated. Each participant then underwent a cardiac gated whole-lung CT scan which was analyzed for the presence of emphysema, interstitial lung abnormalities (ILA), and quantitative airway features. Incident lung disease was determined by a study examiner. The relationship of HOMA-IR to these outcomes was estimated in models adjusted for demographics, body mass index, and lifetime smoking.

Results
875 participants with longitudinal IR data and outcomes were identified. Mean age was 51.5 years and BMI was 26.7 kg/m². HOMA-IR was temporally unstable, with a within-person standard deviation approximately two-thirds of the between-person standard deviation. In adjusted models, a one standard deviation increase in log(HOMA-IR) z-score was associated with higher odds of qualitative emphysema (odds ratio [OR] 1.33; 95% CI 1.04-1.70), interstitial lung abnormalities (OR 1.35; 1.05-1.74), and modest increases in airway wall thickness and wall area percentage. These radiographic findings were corroborated by a positive association of HOMA-IR with incident lung disease.

Conclusions
IR is associated with radiographic lung abnormalities and incident lung disease. Deeper phenotyping is necessary to define mechanisms of IR-associated lung injury.