Early Glucose Abnormalities in Cystic Fibrosis Are Preceded by Poor Weight Gain

OBJECTIVE

Progressive β-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 ≥4.5% detected declining wtSDS with 89% sensitivity and 86% specificity (area under the ROC curve 0.89, P = 0.003). BG_max ≥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} ≥11.1 mmol/l, the decline in wtSDS was worse if BG_max was ≥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 ≥4.5% (−0.3 ± 0.4 vs. 0.1 ± 0.2 for time <4.5%, P = 0.01).

CONCLUSIONS

BG_max ≥8.2 mmol/l on an OGTT and CGM time above 7.8 mmol/l ≥4.5% are associated with declining wtSDS and lung function in the preceding 12 months.Progressive β-cell loss causes catabolism and weight loss in cystic fibrosis (1,2). Weight is a prognostic indicator (3), and prevention of weight decline is a major clinical objective in children and adolescents with cystic fibrosis. Median life expectancy of patients with cystic fibrosis has risen progressively over recent decades but remains drastically shorter (∼36 years) than that of the general population (4). The presence of cystic fibrosis–related diabetes (CFRD) is associated with an increase in early mortality of up to sixfold (5). CFRD is usually diagnosed by the North American Cystic Fibrosis Foundation criteria (6) or World Health Organization (WHO) criteria for diabetes (7). These criteria were designed to identify patients at risk of microvascular complications in type 2 diabetes (8) and were not designed with cystic fibrosis–specific outcomes in mind. Microvascular complications occur in cystic fibrosis (9); however, catabolic decline in weight and deteriorating lung function may be more relevant outcomes. Poor weight gain is associated with worsening lung function (10,11), and both are associated with early mortality (12,13). Weight and lung function declines have been shown to precede the diagnosis of CFRD by standard criteria (2), but the earliest glycemic abnormality associated with clinical decline has not been determined. Glycemic status can be assessed in detail using an oral glucose tolerance test (OGTT) with 30-min samples and, more recently, continuous interstitial fluid glucose monitoring (CGM). We aimed to determine the relationship between glycemic status and the change in weight standard deviation score (wtSDS) and the change in lung function over the preceding year.