(P06-39-26) Relationship of Pro-Inflammatory Cytokines With Body Composition and Glucose Metabolism in Adults With Cystic Fibrosis

Objectives: Chronic systemic inflammation is a distinct characteristic of cystic fibrosis (CF). Highly effective CF transmembrane receptor (CFTR) modulator therapies have led to recent transformational improvements in pulmonary function yet introduced new uncertainties regarding changes in body composition and metabolic health. This study aimed to identify how systemic inflammatory markers relate to adiposity and glucose regulation in people with CF (PwCF) as compared to healthy controls (HC).

Methods: This was a cross-sectional analysis of clinically stable adults with CF (n=65, 54% on a CFTR modulator) and HC (n=44). Serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interferon gamma (IFN-γ), and IL-1β concentrations were assessed with ELISA. DXA-derived body composition and oral glucose tolerance test-derived glucose indices (fasting glucose, HOMA-IR, and Matsuda Index of Insulin Sensitivity) were measured. Group differences were assessed via Mann-Whitney U-tests, and relationships evaluated by Spearman correlations and linear regression with age and sex as covariates.

Results: PwCF had higher serum IL‑6, TNF‑α, and IL‑1β than HC (all p≤0.01). Within PwCF, IFN‑γ was higher in females than males (p=0.01). CFTR modulator use was associated with lower serum IL‑6, TNF‑α, and IL‑1β (all p≤0.04) vs PwCF not on modulators. In PwCF, fasting glucose was inversely correlated with IL‑6, IL‑1β, and IFN‑γ levels, even after adjustment for age and sex. Serum IL‑6 levels correlated inversely with HOMA‑IR and positively with Matsuda Index (all p≤0.04). In HC, fasting glucose correlated inversely with TNF-α and IL‑1β, whereas Matsuda correlated positively with TNF-α (all p≤0.05). In PwCF, serum IL‑6 and IL‑1β levels were inversely associated with BMI, fat mass, fat mass index, and visceral adipose tissue (all p≤0.03), persisting after adjustment. Body fat % was positively associated with serum IL‑6 in HC (p = 0.04).

Conclusions: Adults with CF demonstrated elevated systemic inflammation which attenuated with CFTR modulator therapy. In PwCF, greater systemic inflammation was associated with lower adiposity and decreased fasting glucose and insulin resistance. Longitudinal analyses are needed to better understand the relationship between inflammatory markers, insulin sensitivity, and adiposity in PwCF.

Funding Sources: CF Foundation, NIH