Early glucose abnormalities in children with Cystic Fibrosis

Abstract

Cystic Fibrosis (CF) is frequently complicated by Cystic Fibrosis-related diabetes (CFRD). CFRD has a direct impact on the morbidity of patients with CF and leads to early mortality. However, it is not yet known at what age pre-diabetic “early glucose abnormalities” begin or whether they are clinically important.

The first study of the thesis was to determine whether children with CF less than ten years of age have glucose abnormalities and if present to examine the clinical importance of glucose abnormalities in this cohort that do not have diabetes. I was able to demonstrate that in children with CF, a high intermediate glucose peak on a 5-point Oral Glucose Tolerance Test (OGTT) is negatively correlated with both lung function and nutritional status. The poor clinical status of these children was not predicted by the two-hour level, the current gold standard diagnostic criterion for CFRD. This study also demonstrated that Continuous Glucose Monitoring (CGM) detected a higher frequency of glucose abnormities than the OGTT.

The second part of the thesis evaluated the association between early indicators of airways disease (inflammation) and CGM detected glucose abnormalities in CF. I was able to show that children with pre-diabetic glucose abnormalities on CGM have a greater degree of pulmonary inflammation and were more likely to have a past history of Pseudomonas aeruginosa infection.

In the third study, a longitudinal evaluation of these participants showed for the first time that for most children with CF who exhibit early glucose abnormalities, they will have glucose abnormalities that fluctuate. However, some children will exhibit persistently high glucose levels.

The chapters of this thesis demonstrate for the first time the importance of pre-diabetic CGM detected glucose abnormalities in such young children with CF. These findings suggest that current screening recommendations will miss important, clinically significant glucose abnormalities that may impact on early lung disease in children with CF.