Hypoglycemia in children and young adults with cystic fibrosis during oral glucose tolerance testing vs. continuous glucose monitoring.

Background: Hypoglycemia is common in people with cystic fibrosis (pwCF) during oral glucose tolerance tests (OGTTs) and in the free-living setting, yet its pathophysiology remains unclear.

Objective: To evaluate hypoglycemia in children and young adults with CF by OGTT and continuous glucose monitoring (CGM).

Methods: A 3-h OGTT was performed in children and young adults with CF and healthy controls (HC). Individuals were classified as experiencing hypoglycemia on OGTT (glucose <70 mg/dL) or not. Insulin, C-peptide, glucose, glucagon, and incretins were measured. CGM was performed for 7 days in the free-living setting. Measures of insulin sensitivity, beta cell function accounting for insulin sensitivity, and insulin clearance were calculated.

Results: A total of 57 participants (40 CF and 17 HC) underwent assessment. Rates of hypoglycemia by OGTT were similar in pwCF (53%, 21/40) compared to HC (35%, 6/17), p = 0.23. PwCF compared to HC had higher A1c; on OGTT higher and later glucose peaks, later insulin peaks; and on CGM more glucose variability. CF Hypo+ versus CF Hypo- had higher lung function, higher insulin sensitivity, higher beta cell function accounting for insulin sensitivity, and decreased CGM variability. When comparing CF Hypo+ to HC Hypo+, although rates of hypoglycemia are similar, pwCF had blunted glucagon responses to hypoglycemia. OGTT hypoglycemia was not associated with CGM hypoglycemia in any group.

Conclusion: Youth with CF have increased insulin sensitivity and impaired glucagon response to hypoglycemia on OGTT. Hypoglycemia on OGTT did not associate with free-living hypoglycemia.