Long-Term Insulin Resistance Tied to CT Measures of Interstitial Lung Disease

Long-term insulin resistance is associated with quantitative increases in CT-based measures of interstitial lung disease (ILD), according to findings from a multicenter cohort study presented at the 2026 American Thoracic Society (ATS) International Conference in Orlando, Florida.¹

Insulin Resistance and Interstitial Lung Disease: Study Overview

The analysis, drawn from the Multicenter AIDS Cohort Study (MACS), included 517 men with or at risk for HIV who had both serial insulin resistance measurements and cardiac CT imaging available. Investigators at Johns Hopkins calculated a time-weighted homeostatic model assessment of insulin resistance (HOMA-IR) using up to 5 years of annual measurements prior to CT, capturing cumulative rather than point-in-time exposure.¹

The mean cohort age was 57.5 years, mean BMI was 26.6 kg/m², and mean pack-years was 12.5. Approximately 59.8% of participants were living with HIV, and 8.7% had diabetes. The mean quantitative ILD percentage was 10.6% (SD 9.33).¹

In adjusted models accounting for age, BMI, smoking history, HIV status, race, and medically treated diabetes, each doubling in time-weighted HOMA-IR was associated with a 1.58% greater percentage of lungs with any ILD feature (95% CI, 0.38 to 2.78). The association appeared driven primarily by ground glass opacity (adjusted mean difference 1.43%; 95% CI, 0.44 to 2.43). The relationship with lung fibrosis observed in unadjusted models did not reach statistical significance after adjustment (adjusted mean difference 0.15%; 95% CI, −0.10 to 0.40). No effect modification was found by HIV or diabetes status.¹

In an interview at ATS, investigator Sarath Raju, MD, from Johns Hopkins University, emphasized that cumulative insulin resistance exposure was central to the study’s design.

“Within COPD, we think about someone's pack-years, how long they've smoked over time. We don't just think about how much they smoked that day," Raju said. "We wanted to understand their cumulative exposure to insulin resistance. The time-weighted average gave us a way to think of someone's long-term insulin resistance because we know you don't develop lung disease overnight.”

Ground Glass Findings Point to Metabolic Inflammation

Raju noted that the predominance of ground glass over fibrosis in the findings may carry mechanistic implications. Ground glass opacity can represent active, early pulmonary inflammation rather than established scarring, suggesting insulin resistance may be acting through metabolic inflammation as a precursor to fibrosis rather than a driver of existing structural damage.

The investigators plan to extend the work to larger population-based cohort studies to validate the findings across settings. Raju said mechanistic research is also needed to clarify how systemic insulin resistance, measured peripherally in the blood, produces effects in airway and lung tissue, and whether targeting insulin resistance before the onset of overt diabetes could have a role in lung disease prevention.

"I think once we’ve done that, we can think about whether we should target insulin resistance earlier on, before someone develops overt diabetes, to help prevent that transition from lung health to lung disease,” he said.

SGLT2 Inhibitors Linked to Lower Readmission Risk After AE-COPD Hospitalization

During the meeting, Raju also presented on a retrospective study that found that SGLT2 inhibitors were associated with a 30-day lower readmission risk after acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) hospitalization. The interview with Raju can be viewed here: SGLT2 Inhibitors Linked to Lower Readmission Risk After AE-COPD Hospitalization.²

Raju has no reported disclosures.

References

1. Kortepeter D, Brown T, Kunisaki K, et al. (Poster Board # P1801). Long-Term Insulin Resistance Is Associated With Increases in Quantitative CT Measures of Interstitial Lung Disease." Poster presented at ATS 2026 on May 19 in Orlando, Florida.

2. Raju S. SGLT2 Inhibitors Linked to Lower Readmission Risk After AE-COPD Hospitalization. HCPLive. Published May 27, 2026. Accessed June 10, 2026. https://www.hcplive.com/view/sglt2-inhibitors-linked-lower-readmission-risk-copd-hospitalization