Estey Mathew P, Sissons Shelby, Sharpe Heather, Doll-Shankaruk Michelle, Beriault Dan, Gilmour Julie, Lee Kathleen, Leung Winnie, Parkins Michael D, Quon Bradley S, Tullis Elizabeth, Zheng Jie, Lam Grace Y
Alberta Precision Labs, Edmonton, Alberta, Canada.
Department of Laboratory Medicine and Pathology, University of Alberta, Canada.
Ann Med. 2025 Dec;57(1):2514787. doi: 10.1080/07853890.2025.2514787. Epub 2025 Jun 5.
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 ppFEV ( < 0.0001), while the OGTT was inversely correlated with ppFEV ( < 0.05), and the fructosamine-to-albumin ratio was inversely correlated with BMI (-0.9; 95% CI -1.5, -0.4; = 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 ppFEV than the OGTT, consideration could be made to redefine CFRD based on HbA1c.
随着囊性纤维化(CF)患者预期寿命的延长,与CF相关的并发症,如CF相关糖尿病(CFRD),备受关注。口服葡萄糖耐量试验(OGTT)是目前筛查CFRD的金标准试验,CFRD与肺功能和体重指数(BMI)降低有关。然而,这是一项繁琐且依从性差的试验,新出现的证据表明糖化血红蛋白(HbA1c)或血清果糖胺可能是可行的替代筛查工具。
在加拿大四个成人CF中心开展了一项多中心研究,以确定HbA1c和血清果糖胺水平预测OGTT筛查结果的能力。收集了横断面结局数据,包括检测后两个月内的ppFEV1和BMI。
共纳入了五年内183次CFRD筛查病例。根据OGTT定义的临界值,HbA1c和果糖胺与白蛋白比值对CFRD的预测性能相似(AUC均为0.68);对糖耐量受损的预测性能也相似(AUC分别为0.69和0.64)。然而,果糖胺与白蛋白比值的特异性较低,这意味着在筛查CFRD和/或糖耐量受损时,与HbA1相比,若将果糖胺与白蛋白比值用作第一步筛查试验,可避免进行OGTT的患者更少。CFRD筛查的最佳HbA1c临界值为≥5.5%(敏感性95%;特异性32%)。回归分析表明HbA1c与ppFEV之间存在强负相关(<0.0001),而OGTT与ppFEV呈负相关(<0.05),果糖胺与白蛋白比值与BMI呈负相关(-0.9;95%CI -1.5,-0.4;P=0.002),但与检测后2个月内的ppFEV1无关。
HbA1c被证实可作为CFRD筛查的第一步,可使三分之一的患者避免进行OGTT。由于HbA1c与ppFEV的相关性比OGTT更强,可考虑基于HbA1c重新定义CFRD。