Isolated Hypoglycemia in Children with Cystic Fibrosis: Role of Pancreatic Insufficiency and Glucagon Response

Objective: Hypoglycemia is one of the comorbidities that adversely affects the quality of life in patients with cystic fibrosis (CF). Isolated hypoglycemia (IsoHypo) is poorly described in patients with CF and its etiopathogenic significance is unclear. To investigate the etiopathogenesis of IsoHypo and the role of pancreatic insufficiency (PI) in IsoHypo in children with CF. Methods: The blood glucose, insulin, and glucagon responses of patients with CF and healthy controls were evaluated during a 3-hour oral glucose tolerance test. Based on the results, the patients were categorized into 5 groups: 1) normal glucose tolerance (NGT); 2) IsoHypo; 3) hypoglycaemia with abnormal glucose tolerance (Hypo+AGT); 4) AGT; and 5) CF-related diabetes. IsoHypo and NGT were sub-classified according to the presence of PI as PI(+) or PI(-). Hypoglycemia was defined as blood glucose <70 mg/dL. Results: A total of 44 patients with CF and 9 controls. Hypoglycaemia was observed in 21 of 44 patients (47.7%), predominantly as IsoHypo (29.5%). Hypo+AGT was found in eight patients (18.2%). The IsoHypo group exhibited undelayed and higher insulin secretion than the Hypo+AGT group, with IsoHypo PI(-) being less impaired compared to IsoHypo PI(+). Both IsoHypo and Hypo+AGT groups exhibited a blunted rise in glucagon at 180 minutes, with the deficiency being more pronounced in the Hypo+AGT group. Insulin and glucagon responses to oral glucose load in IsoHypo PI(+) were similar to Hypo+AGT, whereas they were less impaired in IsoHypo PI(-) patients who had early and higher insulin secretion. Conclusion: IsoHypo is common in children with CF and may precede Hypo+AGT in those with PI(+). The abnormal insulin and glucagon responses to glucose appear to be the most significant contributors to the development of IsoHypo in CF.