Facteurs métaboliques, nutritionnels, anthropométriques et pulmonaires associés à l’apparition d’anomalies du métabolisme du glucose dans une cohorte d’enfants avec fibrose kystique

Introduction: Cystic fibrosis (CF) is the leading cause of mortality among Canadian children and young adults caused by genetic disease. Cystic Fibrosis-Related Diabetes (CFRD) has been identified as one of the most important comorbidities, increasing the risk of mortality by six-fold. Knowledge on the clinical signs related to the onset of glucose tolerance abnormalities, such as CFRD, impaired glucose tolerance (IGT) and indeterminate status (INDET) is very limited in the CF pediatric population. Hypothesis: We postulate that some clinical parameters are associated with the occurrence of glucose tolerance abnormalities (IGT/INDET/CFRD) in children and adolescents with CF. Objectives: 1) To document the longitudinal evolution of some clinical parameters from the initial diagnosis of CF to the diagnosis of glucose tolerance abnormalities. 2) To identify clinical markers associated with the occurrence of IGT/INDET/CFRD. Methodology: Retrospective study of medical records of patients followed at the CHU Sainte-Justine CF Clinic between 1983 and 2018. Data were collected from the diagnosis of CF until the onset of glucose tolerance abnormalities (IGT/INDET/CFRD groups) or until the last follow-up visit prior to transfer to adult care (normoglycemic group (NGT)). Results of the oral glucose tolerance test (OGTT) were used to determine the presence of glucose tolerance abnormalities. The collected variables were metabolic (HbA1c, blood glucose and insulin levels pre and two hours post-OGTT), nutritional (serum retinol (vitamin A), alpha-tocopherol (vitamin E) and 25-hydroxyvitamin D (vitamin D)), anthropometric (weight, height) and pulmonary (first-second forced expiratory volume (FEV1), forced vital capacity (FVC)). Descriptive statistics, Kaplan-Meier analysis, and Cox regression models were used to compare variables between the IGT/INDET/CFRD groups and the NGT group. Results: Among the 281 included children, 75 were classified as IGT, 28 as INDET, 51 as CFRD and 127 as NGT. No marked differences were observed in the longitudinal evolution of nutritional variables (vitamin A, E and D) and pulmonary variables (FVC and FEV1). However, the trajectories of metabolic variables (HbA1c and glycemia two hours post-OGTT) and anthropometric variables (height and weight Z-scores) differed between the IGT/INDET/CFRD groups and the NGT group. An increase in HbA1c was associated with the occurrence of CFRD (HR 2.406, 95% CI [1.923; 3.010]) and INDET (HR 1.657, 95% CI [1.192; 2.303]), but not IGT. An increase in the Z-score of height decreased the risk of developing CFRD (HR 0.496, 95% CI [0.325; 0.756]). Age at the time of CF diagnosis, sex, exocrine pancreatic status, and CF gene mutations did not influence the occurrence of glucose tolerance abnormalities. Conclusion: Our results suggest that several clinical parameters are associated with the occurrence of glucose tolerance abnormalities. In addition to those currently used to monitor the development of CFRD (weight, height, FVC and FEV1), we found that other parameters are associated with the occurrence of glucose tolerance abnormalities (HbA1c). The identification of clinical precursors may allow early management of CFRD and potentially prevent progression of the disease.

Keyphrases: cystic fibrosis, diabetes, weight, height, lung function, vitamins, blood glucose, children