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

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.

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.

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).

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.