Sarath Raju, MD, from Johns Hopkins University School of Medicine.

Sarath Raju, MD

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 

, according to findings from a multicenter cohort study presented at the 

2026 American Thoracic Society (ATS) International Conference

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.

The study used up to 5 years of serial HOMA-IR measurements to calculate cumulative insulin resistance exposure via time-weighted average

Each doubling in long-term insulin resistance associated with 1.58% increase in quantitative interstitial lung disease on computed tomography

Ground glass opacity—a potential marker of early pulmonary inflammation—drove the CT association; lung fibrosis link did not persist after adjustment

Findings held regardless of HIV or diabetes status

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).

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.

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

Kortepeter D, Brown T, Kunisaki K, et al. (

). 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.

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

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Sarath Raju, MD, discussed a study that found persistent IR was associated with higher ground glass opacity on CT, suggesting metabolic inflammation may drive early ILD development.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors were associated with lower 30-day readmission risk among diabetic patients hospitalized for acute exacerbations of 

 (AE-COPD), according to findings presented at the 

2026 American Thoracic Society (ATS) International Conference 

 Sarath Raju, MD, from Johns Hopkins University School of Medicine, highlighted the growing importance of cardiometabolic management in COPD care, emphasizing that the disease extends beyond the lungs and frequently overlaps with cardiovascular disease, heart failure, insulin resistance, and diabetes. He also noticed that drugs for cardiometabolic health may also improve outcomes for patients with COPD.

The retrospective cohort analysis evaluated 11,610 AE-COPD admissions among diabetic individuals receiving diabetes medications across 10 hospitals in Minnesota between 2011 and 2024. Investigators examined whether prescriptions for SGLT2 inhibitors or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were associated with a lower risk for 30-day readmission or death compared with other diabetes therapies.

Among the cohort, 514 patients were receiving SGLT2 inhibitors, and 587 were prescribed GLP-1 receptor agonists. The composite endpoint of 30-day readmission or death occurred in 15.8% of patients receiving SGLT2 inhibitors, 15.7% on GLP1-RA, and 19.8% in those receiving other diabetes medications.

After multivariable adjustment, SGLT2 inhibitor use was associated with significantly lower odds of the composite outcome (adjusted odds ratio [aOR], 0.71; 95% CI, 0.55 to 0.91) and lower odds of 30-day readmission alone (aOR, 0.74; 95% CI, 0.57 to 0.95). Time-to-event analyses similarly suggested reduced risk among patients receiving SGLT2 inhibitors.

Although GLP-1 receptor agonists demonstrated trends toward benefit (composite aOR 0.85, 95% CI, 0.67 to 1.07 and 30-day readmission aOR 0.83, 95% CI, 0.65 to 1.06), associations did not reach statistical significance.

He added that the relationship between diabetes and pulmonary disease may be bidirectional, with emerging evidence suggesting insulin resistance and metabolic syndrome may directly worsen lung health. Ruju said that future research needs to examine whether treatment for diabetes could improve lung health.

He also said future investigations should determine whether the apparent benefit stems primarily from reduced cardiovascular events, direct pulmonary effects, or broader systemic improvements. Raju emphasized the need for more mechanistic and prospective studies before cardiovascular health interventions can be incorporated into post-exacerbation COPD treatment strategies.

“Are these [medications] reducing cardiovascular events after hospitalization? Are they [first] reducing the risk for COPD exacerbations?” he wondered.

Raju noted that the findings reinforce growing recognition that COPD management requires attention to systemic disease processes and cardiometabolic health.

“We’re trying to move away from treating COPD as a disease that affects one organ,” Raju said. “[COPD] affects multiple organs, and…people with COPD are often more likely to die from cardiovascular causes.”

Macdonald D, Dransfield M, Henkle B, et al. (

) SGLT2 Inhibitors Are Associated With Decreased Risk of 30-Day Readmission in Diabetic Individuals Hospitalized for Acute Exacerbations of COPD: A Retrospective Cohort Analysis. Poster presented at ATS 2026 in Orlando, Florida, on May 18.

At ATS 2026, Sarath Raju, MD, discussed retrospective data linking SGLT2 inhibitor use to reduced 30-day readmissions in patients hospitalized for AE-COPD and diabetes.

Sarath Raju, MD

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