Screening for cystic fibrosis‐related diabetes and prediabetes: Evaluating 1,5‐anhydroglucitol, fructosamine, glycated albumin, and hemoglobin A1c

Abstract

Objective Dysglycemia is prevalent in cystic fibrosis (CF) but screening with annual oral glucose tolerance tests (OGTT) can be burdensome. We investigated alternate glycemic markers—hemoglobin A1c (HbA1c), 1,5‐anhydroglucitol (1,5AG), fructosamine (FA), and glycated albumin (GA)—as screening tests for CF‐related diabetes (CFRD) and pre‐diabetes (CFPD) in youth with CF as defined by the gold‐standard OGTT 2‐hour glucose (2hG). Methods Youth 10 to 18 years with CF had a 1,5AG, FA, GA, HbA1c, and 2‐hour OGTT collected. Correlations between all glycemic markers and 2hG were evaluated. Area under the receiver operative characteristic (ROC‐AUC) curves were generated. Optimal cut points for predicting CFPD (2hG ≥ 140 mg/dL) and CFRD (2hG ≥ 200 mg/dL) were determined. Results Fifty‐eight youth with CF were included (2hG < 140, n = 16; CFPD, n = 33; CFRD, n = 9; 41% male, mean ± SD age 14.2 ± 3.6 years, BMI z‐score 0.0 ± 0.8, % predicted forced expiratory volume in 1 second [FEV1] 89.9 ± 15.1, % predicted forced vital capacity [FVC] 103.2 ± 14.6). ROC‐AUC's for all alternate markers were low for CFPD (0.52‐0.67) and CFRD (0.56‐0.61). At a cut point of 5.5%, HbA1c had 78% sensitivity (95% CI: 0.45‐0.94) and 41% specificity (95% CI: 0.28‐0.55) for identifying CFRD, correlating to a ROC‐AUC of 0.61 (95% CI: 0.42‐0.8). Conclusions All alternate markers tested demonstrate poor diagnostic accuracy for identifying CFRD by 2hG.

Screening Methods for Diagnosing Cystic Fibrosis-Related Diabetes: A Network Meta-Analysis of Diagnostic Accuracy Studies

“…We included 31 studies (26 full-text papers and 5 conference abstracts) in the network meta-analysis ([ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ]). The selection process is shown in Figure 1 .…”

“…In the index test domain of QUADAS-2, three records were deemed as having a high risk of bias. In these articles, the authors defined cut-off values for the index tests based on the OGTT results [27,32,40]. The reference standard domain was considered at a low risk of bias in all but one case [41].…”

Diabetes in Patients With Ataxia Telangiectasia: A National Cohort Study

“…This shows that the OGTT is still of value and confirms the current recommendation of the English CF society: HbA1c reflects glycemic control over a period of time. The statement about the long-term course of blood glucose has some advantages, but the values of HbA1c in CF patients may still be within the normal range when the OGTT already shows an IR or even diabetes (55). Taken these information into account, we truly believe that both measurements, HbA1c and OGTT, should be applied in A-T patients.…”

Detection and Management of Early Glucose Abnormalities in Cystic Fibrosis

“…It usually reflects average blood glucose over the life of an erythrocyte (~3 months) [64,69]. However, CF patients with CFRD, INDET or IGT rarely have a significantly-higher HbA 1c than those with normal glucose tolerance (NGT) [11,[70][71][72][73], and even statisticallysignificant differences tend to be of <1% magnitude [8,34,40,74,75]. Godbout et al's study of 13 CFRD patients also found that HbA 1c did not correlate with mean plasma glucose, as calculated using fingerprick self-monitoring [76].…”

“…Lowering the diagnostic threshold for HbA 1c abnormalities does increase sensitivity to both CFRD and AGT, but the thresholds required to achieve sufficient sensitivity for screening generally have unacceptably low specificity [60]. There is also wide variation in the sensitivities and specificities reported by different studies using the same HbA 1c threshold; this may be due to differences in type of HbA 1c assay [74,86] and timing of the studies relative to the institution's routine OGTT screening [87]. Yung et al, conducting a cross-sectional study of 91 CF patients not known to be diabetic, but also not previously routinely screened, found that HbA 1c ≥6.1% had 83% sensitivity for OGTT-diagnosed CFRD [68].…”