Once daily insulin detemir in cystic fibrosis with insulin deficiency.

The aim of this study was to determine if once daily insulin detemir reverses decline in weight and lung function in patients with cystic fibrosis (CF). 12 patients with early insulin deficiency and six with CF related diabetes (aged 7.2-18.1 years) were treated for a median of 0.8 years. Changes in weight and lung function following treatment were compared to pretreatment changes. Before treatment, the change in weight SD score (ΔWtSDS), percentage of predicted forced expiratory volume in 1 s (Δ%FEV(1)) and percentage of predicted forced vital capacity (Δ%FVC) declined in the whole study population (-0.45±0.38, -7.9±12.8%, -5.8±14.3%) and in the subgroup with early insulin deficiency (-0.41±0.43, -9.8±9.3%, -6.8±10.3%). Following treatment with insulin ΔWtSDS, Δ%FEV(1) and Δ%FVC significantly improved in the whole study population (+0.18±0.29 SDS, p=0.0001; +3.7±10.6%, p=0.007; +5.2±12.7%, p=0.013) and in patients with early insulin deficiency (+0.22±0.31 SDS, p=0.003; +5.3±11.5%, p=0.004; +5.8±13.4%, p=0.024). Randomised controlled trials are now needed.

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

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.