Screening for Cystic Fibrosis–Related Diabetes and Prediabetes—Evaluating 1,5-Anhydroglucitol, Fructosamine, Glycated Albumin, and Hemoglobin A1c

Abstract

Dysglycemia in the cystic fibrosis (CF) population is widespread and screening via oral glucose tolerance tests (OGTT) can be burdensome. Our primary aim was to investigate 1,5-anhydroglucitol (1,5AG), fructosamine (FA), glycated albumin (%GA), and hemoglobin A1c (HbA1c) as screening tests for cystic fibrosis-related prediabetes (CFPD) and cystic fibrosis-related diabetes (CFRD) in youth with CF as defined by the OGTT 2-hour glucose (2hG). Our secondary aim was to determine if alternate screening tests can identify those with better or worse lung function (forced expiratory volume in 1 second, FEV1%; forced vital capacity, FVC%). Youth 10-18 years with CF had 1,5AG, FA, %GA, HbA1c, and a 2 hour OGTT collected during a single study visit. Pearson’s correlation coefficient determined the correlation between all 4 glycemic estimates and 2hG. Receiver Operative Characteristic (ROC) curves were generated. The Youden Index determined optimal cut points for predicting CFPD (2hG≥140-200 mg/dL) and CFRD (2hG≥200 mg/dL). Lung function measures above and below these cutpoints were compared. Fifty-eight youth with CF participated (2hG<140, n=31; CFPD, n=17; CFRD, n=10; mean age 14±3.5 years, 43% male, BMI z-score 0.0±0.8, FEV1% 90±15.0, FVC% 99±14.1). FA, %GA, and HbA1c correlated with 2hG (p-<0.05). ROC area under the curves (ROC-AUCs) for all 4 alternate markers were low for both CFPD (0.53-0.67) and CFRD (0.56-0.66). HbA1c had the highest ROC-AUC of 0.66 (95% CI: 0.47-0.84) for identifying CFRD and 0.67 (95% CI: 0.53-0.8) for CFPD. When lung function was compared stratifying above and below the Youden cutpoint for CFRD, only HbA1c identified significant differences in FVC% (105% vs. 96%, p=0.02); FEV1% was not statistically significant (96% vs. 88%, p=0.06). All 4 alternate markers had poor diagnostic accuracy for identifying CFRD by 2hG, although HbA1c may be useful in detecting CFPD and in stratifying individuals with CF by lung function. Disclosure K.L. Tommerdahl: None. J.T. Brinton: None. T.B. Vigers: None. K.J. Nadeau: None. P. Zeitler: Consultant; Self; Daiichi Sankyo Company, Limited, Merck & Co., Inc., Eli Lilly and Company, Takeda Development Center Americas, Inc., Boehringer Ingelheim GmbH. C.L. Chan: None.