Abstract Rationale Insulin resistance (IR) has been identified as a risk factor for multiple chronic health conditions, though its association with lung disease is understudied. Metabolic inflammation and oxidative stress from IR may enhance risk for interstitial lung disease (ILD), though the association between ILD and IR is unknown. Persons with HIV face higher rates of both insulin resistance and ILD, which may provide a unique opportunity to investigate the association between IR and ILD. Methods Clinical and CT data from the Multicenter AIDS Cohort Study (MACS) of men with or at risk for HIV were utilized. Participants underwent serial measurements of IR, from which we calculated a time-weighted (TW) HOMA-IR based on the trapezoidal method to represent long-term IR. This analysis incorporated up to 5 years of annual HOMA-IR measurements prior to CT. Participants subsequently underwent cardiac CT imaging where established textural analysis methods were applied to quantify ILD patterns, including the percentage of the lung with any ILD feature (QILD) and specific patterns (ground glass, lung fibrosis). Linear regression models analyzed relationships between TW-HOMA-IR and CT abnormalities after adjusting for age, BMI, smoking status, pack-years, HIV status, race, education, scanner model, and medically-treated diabetes. Interaction models assessed effect modification by diabetes and HIV status. IR measures were log2 transformed with results described per doubling in HOMA-IR. Results The analysis included 517 men with CT and IR data. Mean age was 57.5 years, BMI was 26.6 kg/m2, and pack-years was 12.5 years. 309 (59.8%) participants were men with HIV and 45 (8.7%) had diabetes. Participants had a mean QILD percentage of 10.6 (SD 9.33). In adjusted analyses, higher TW-HOMA-IR was associated with higher QILD percentage (adjusted mean difference aMD 1.58%; 95% CI 0.38, 2.78) which appeared to be driven by a higher prevalence of ground-glass (aMD 1.43%; 95% CI 0.44, 2.43). TW-HOMA-IR was associated with a difference in % fibrosis in crude models which was no longer statistically significant after adjustment (aMD 0.15%; 95% CI -0.10, 0.40). There was no effect modification by HIV or diabetes status. Conclusions Findings from a multi-center cohort study demonstrate an association between persistent insulin resistance and higher interstitial lung abnormalities. The results with ground glass but not fibrosis suggest that differences may be explained by active metabolic inflammation as a driver of IR-associated lung disease. Future research is needed to validate this finding and to explore the underlying mechanisms. This abstract is funded by: NHLBI
Kortepeter et al. (Fri,) studied this question.