(4) Role of Hyperglycemia in Cystic Fibrosis Pulmonary Exacerbations

Background: Hyperglycemia could affect treatment response during cystic fibrosis (CF) pulmonary exacerbations (PEx). We aimed to evaluate hyperglycemia prevalence during CF PEx, associations of hyperglycemia with PEx outcomes, and feasibility of continuous glucose monitoring (CGM) during PEx.

Methods: The STOP2 study was a multicenter randomized clinical trial evaluating the efficacy and safety of different durations of intravenous (IV) antibiotics for PEx among adults with CF [1]. We conducted an ancillary study to STOP2. Random glucose levels measured clinically during the first 7-10 days of the PEx treatment were captured. A subset of participants at 4 sites also consented to undergo CGM for 5 days, beginning at IV antibiotic day 1-4. Associations between hyperglycemia, defined as random glucose >140 mg/dL, and changes in weight and lung function between baseline (initiation of IV treatment) and visit 2 (day 7-10), and visit 3 (14 days following completion of IV treatment) were evaluated with linear regression after adjustment for confounders.

Results: Random glucose measurements were available for 182 STOP2 participants (18.6% of 982 randomized in STOP2). Among these participants, 37% had CF related diabetes (CFRD), 27% were on insulin, mean (SD) age was 31.6 (10.8) years and mean (SD) baseline percent predicted (pp) FEV1 was 53.6 (22.5). Hyperglycemia was detected in 44% of these participants; 61% of those with hyperglycemia had a diagnosis of CFRD. Table 1 shows the mean estimated differences differences (95% CI) in changes in ppFEV₁ and weight (kg) from baseline to visit 2 and visit 3, between those with and without hyperglycemia, and on insulin or not. No differences were detected by hyperglycemia or by insulin use at visit 2 or visit 3.

Ten participants who were not on insulin or oral hypoglycemic agents in the 4 weeks prior to study underwent CGM. Mean (SD) age was 30.1 (6.5) years, 70% female and mean (SD) baseline ppFEV1 was 48.9 (21.0)). Mean (SD) time >140 mg/dL was 24.6% (12.5) and 9/10 participants spent >4.5% time >140 mg/dL.

Conclusions: Hyperglycemia identified with random glucose was prevalent during CF PEx in patients with and without CFRD, but we did not detect an association between hyperglycemia and changes in lung function or weight with treatment. CGM is feasible and may provide a useful tool in the inpatient setting.

Acknowledgements: This work was supported by the CF foundation [MERJAN17ABO, MERJA19GE0].

References: [1] Goss, C.H., et al., A Randomized Clinical Trial of Antimicrobial Duration for Cystic Fibrosis Pulmonary Exacerbation Treatment. Am J Respir Crit Care Med, 2021. 204(11): p. 1295-1305.