Early glucose abnormalities in cystic fibrosis are preceded by poor weight gain

Abstract

Objective: Progressive beta-cell loss causes catabolism in cystic fibrosis. Existing diagnostic criteria for diabetes were based on microvascular complications rather than on cystic fibrosis-specific outcomes. We aimed to relate glycemic status in cystic fibrosis to weight and lung function changes.

Research design and methods: We determined peak blood glucose (BG(max)) during oral glucose tolerance tests (OGTTs) with samples every 30 min for 33 consecutive children (aged 10.2-18 years). Twenty-five also agreed to undergo continuous glucose monitoring (CGM) (Medtronic). Outcome measures were change in weight standard deviation score (wtSDS), percent forced expiratory volume in 1 s (%FEV1), and percent forced vital capacity (%FVC) in the year preceding the OGTT.

Results: Declining wtSDS and %FVC were associated with higher BG(max) (both P = 0.02) and with CGM time >7.8 mmol/l (P = 0.006 and P = 0.02, respectively) but not with BG(120 min). A decline in %FEV1 was related to CGM time >7.8 mmol/l (P = 0.02). Using receiver operating characteristic (ROC) analysis to determine optimal glycemic cutoffs, CGM time above 7.8 mmol/l > or =4.5% detected declining wtSDS with 89% sensitivity and 86% specificity (area under the ROC curve 0.89, P = 0.003). BG(max) > or =8.2 mmol/l gave 87% sensitivity and 70% specificity (0.76, P = 0.02). BG(120 min) did not detect declining wtSDS (0.59, P = 0.41). After exclusion of two patients with BG(120 min) > or =11.1 mmol/l, the decline in wtSDS was worse if BG(max) was > or =8.2 mmol/l (-0.3 +/- 0.4 vs. 0.0 +/- 0.4 for BG(max) <8.2 mmol/l, P = 0.04) or if CGM time above 7.8 mmol/l was > or =4.5% (-0.3 +/- 0.4 vs. 0.1 +/- 0.2 for time <4.5%, P = 0.01).

Conclusions: BG(max) > or =8.2 mmol/l on an OGTT and CGM time above 7.8 mmol/l > or =4.5% are associated with declining wtSDS and lung function in the preceding 12 months.

Figures

Figure 1

Glucose and insulin levels during the OGTT. Boxes show the median and interquartile range. Whiskers show the 5th and 95th percentiles.

Figure 2

Decline in wtSDS over the preceding year by BGmax on an OGTT (A) and by percentage of CGM time above 7.8 mmol/l (B). The vertical lines at 8.2 mmol/l and 4.5% CGM time above 7.8 mmol/l represent optimal cutoffs determined by the ROC analysis in Fig. 3.

Figure 3

Determination of optimal glycemic cut points for detecting decline in wtSDS over the preceding 12 months by ROC analysis. A: Plot of sensitivity vs. false-positive rate (1 − specificity) for all possible cut points in BGmax by OGTT. The point closest to the top left-hand corner (8.2 mmol/l) maximizes sensitivity and specificity and is the optimal cut point. B: Percentage of CGM time above 7.8 mmol/l with the optimal cut point of 4.5%. C: Same data for BG120 min on OGTT, which did not detect declining wtSDS. The cut point of 11.1 mmol/l used in the WHO diagnostic criteria is marked.