Time to replace the oral glucose tolerance test for cystic fibrosis related diabetes first-step screening? Establishing glycemic tools relevant to cystic fibrosis

As the life expectancy of people with cystic fibrosis (CF) increases, complications related to CF, such as CF-related diabetes (CFRD), are of great concern. Oral glucose tolerance test (OGTT) is the current gold standard test to screen for CFRD, which is associated with reduced lung function and body mass index (BMI). However, this is a cumbersome test with poor adherence, and emerging evidence suggests that HbA1c or serum fructosamine might be viable alternative screening tools. A multi-center study across four Canadian adult CF centers was conducted to determine the ability of HbA1c and serum fructosamine levels to predict screening OGTT results. Cross-sectional outcome data, including ppFEV1 and BMI within two months of testing, were collected. A total of 183 CFRD screening encounters over five years were included. HbA1c and the fructosamine-to-albumin ratio had similar predictive performances for CFRD as determined by OGTT-defined cutoffs (AUC both 0.68) and for impaired glucose tolerance (AUC 0.69 and 0.64, respectively). However, the specificity of FAR is lower, meaning fewer OGTTs can be avoided if FAR is used as a first-step screening test when screening for either CFRD and/or IGT compared to HbA1. The optimal HbA1c cut-off for CFRD screening was ≥5.5% (sensitivity, 95%; specificity, 32%). Regression analyses demonstrated a strong inverse correlation between HbA1c and ppFEV1 (p < 0.0001), while the OGTT was inversely correlated with ppFEV1 (p < 0.05), and the fructosamine-to-albumin ratio was inversely correlated with BMI (–0.9; 95% CI −1.5, −0.4; p = 0.002), but not with ppFEV1 within 2 months of testing. HbA1c is validated as a first step in screening for CFRD, allowing one-third of the patients to avoid the OGTT. As HbA1c demonstrated a stronger correlation with ppFEV1 than the OGTT, consideration could be made to redefine CFRD based on HbA1c. What is already known on this topic—The current gold standard for screening for CFRD is the oral glucose tolerance test (OGTT). However, the test has poor patient adherence; recently, alternative approaches are suggested.What this study adds – This study suggests that screening for CFRD with an HbA1c test may be a viable first step in reducing the OGTT burden for patients.How this study might affect research, practice or policy: This study provides strong evidence for the use of HbA1c as a first step in the screening algorithm for CFRD, reducing the need for OGTT. What is already known on this topic—The current gold standard for screening for CFRD is the oral glucose tolerance test (OGTT). However, the test has poor patient adherence; recently, alternative approaches are suggested. What this study adds – This study suggests that screening for CFRD with an HbA1c test may be a viable first step in reducing the OGTT burden for patients. How this study might affect research, practice or policy: This study provides strong evidence for the use of HbA1c as a first step in the screening algorithm for CFRD, reducing the need for OGTT.

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