(14) Preservation of body composition in adolescents and young adults with Cystic Fibrosis

Background: In people with Cystic Fibrosis (pwCF), pulmonary function has traditionally been positively correlated with body mass index (BMI) and negatively associated with the diagnosis of diabetes (CFRD). Existing literature posits that the association between BMI and FEV₁%-predicted is mediated by lean body mass (LBM). We hypothesized that deficits in LBM accrual exist in adolescents and young adults with CF and are worse with glucose intolerance.

Methods: Body composition was measured by whole body DXA in non-diabetic pwCF and sex-, age- and BMI-matched healthy controls (HC) who participated annually in 3 study visits between May 2016-Jan 2022. 75-gram oral glucose tolerance test (OGTT) was performed in pwCF. LBM, appendicular LBM and fat mass indices (LBMI=LBM/height², ALBMI=appendicular LBM/ height²
and FMI=FM/height²) were calculated. Mixed effects models were used to estimate accrual of body composition indices among groups adjusted for sex and age and using an interaction term for group and time. The association between body composition indices and OGTT glucose were also tested using mixed effects models, again adjusting for sex and age.

Results: 26 pwCF (14 male, median age 19.8Y (range: 16.5-23.2), 20 pancreatic insufficient, median FEV₁%-predicted 98 (71-130), BMI 25.1 kg/m²(18.0-34.3)) and 24 HC (12 male, 20.8Y (16.6-23.1), BMI 24.1 kg/m²(19.9-33.8)) were followed for 25.5 (0-40.2) and 24.1 months (0-39.7), respectively. Follow-up data were available for 24 CF and 18 HC. At baseline, fasting blood glucose (FBG) was 91 mg/dL(80-112), OGTT 1-hr glucose 175(97-329) and OGTT 2-hr glucose 107 (36-162). Glucose tolerance worsened for 7 pwCF; two of whom developed CFRD, were initiated on insulin therapy, and then censored from analyses. 15 pwCF were treated with CFTR modulator during the study (4 on Elexacaftor-tezacaftor-ivacaftor). At baseline, LBMI (15.8 kg/m²(13.7-23.7) vs 15.5 (12.6-24.2), P=0.7), ALBMI (6.9 kg/m² (5.4-10.3) vs 6.8 (5.3-11.5), P=0.7) and FMI (6.4 kg/m²(3.1-12.3) vs 7.5 (3.2-12.8), P=0.5) did not differ between CF and HC. Over the study period, LBMI (P=0.8), ALBMI (P=0.2) and FMI (P=0.1) did not change in the study population. LBMI accrual, adjusted for sex and baseline age, was similar among CF and HC (P=0.6), as was ALMBI accrual (P=0.5). Similarly, no group differences in FMI accrual were found (P=0.3). Further adjustment for BMI did not result in group differences in indices. Among CF males and females, LBMI over time was not associated with increasing FBG (P=0.8), OGTT 1-hr glucose (P=0.9), or OGTT 2-hr glucose (P=0.9). ALBMI and FMI accrual were also not associated with FBG and OGTT 1- and 2-hr glucose (P >0.1 for all). Use of CFTR modulator was not associated with changes in LBMI, ALBMI or FMI among CF (P >0.1 for all).

Conclusions: Over a two-year period, body composition in pwCF remained stable and was comparable to non-CF individuals. This small CF cohort also demonstrated a lack of association between body composition and early glucose intolerance or CFTR modulator therapy. With overall advancements in CF care and improved lung function and nutritional status, a subgroup of pwCF may be less vulnerable to the traditional relationship of nutrition decline with glucose intolerance and may experience no additional gain in LBM with CFTR modulator use.

Acknowledgements: This work was supported by Public Health Service research grants NIDDK K23 DK107937 (to S.S) and UL1 TR001878 (University of Pennsylvania Centers for Human Phenomic Science)

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