(DCP021) A GLYCOSYLATED HEMOGLOBIN ABOVE 6% IS ASSOCIATED WITH A HIGH RISK OF DEVELOPING CYSTIC FIBROSIS-RELATED DIABETES AND A LOWER PROBABILITY OF WEIGHT GAIN IN BOTH ADULTS AND CHILDREN WITH CYSTIC FIBROSIS

Background: The classical glycosylated hemoglobin (A1c) threshold of 6.5% is an insensitive screening test for cystic fibrosis (CF)-related diabetes (CFRD). We sought to identify CF-specific A1c thresholds associated with 1) risk of progression to CFRD and 2) changes in body mass index (BMI) and forced expiratory volume (FEV1).

METHODS AND RESULTS: We studied the cross sectional and longitudinal associations between A1c, BMI, and FEV1 in 2 cohorts of 223 children (followed for up to 8 years) and 289 adults (followed for a mean of 7.5 ± 4.3 years) with CF but without diabetes at baseline and undergoing regular assessments including Oral Glucose Tolerance Test (OGTT).
For the onset of OGTT-defined CFRD, optimal A1c threshold was 5.9% in adults (sensitivity: 67% and specificity: 71%) and 5.7% for children (sensitivity: 60% & specificity: 47%).
Kaplan-Meier analysis of progression to CFRD according to baseline A1c showed an increased risk of developing CFRD for A1c ≥ 6.0% in adults (p=0.002) and ≥ 5.5 % in children (p=0.012).
Temporal changes in BMI and FEV1 according to baseline A1c in adults were assessed with a linear mixed-effect model. BMI significantly increased over time in subjects with a baseline A1c < 6.0%, but those with an A1c ≥ 6.0% gained significantly less weight over time (p = 0.05). There was no difference in FEV1 according to baseline A1c category.

Conclusion: An A1c above 6% may be associated with a high risk of developing CFRD and a lower probability of weight gain in both adults and children with CF.