Abstract
BACKGROUND: The glycemic characterization of congenital hyperinsulinism (HI), a rare disease causing severe hypoglycemia in childhood, is incomplete. Continuous glucose monitoring (CGM) offers deep glycemic phenotyping to understand disease burden and individualize patient care. Typically, CGM has been restricted to severe HI only, with performance being described in short-term, retrospective studies. We have described CGM-derived phenotyping in a prospective, unselected national cohort providing comprehensive baseline information for future therapeutic trials. METHODS: Glycemic frequency and trends, point accuracy, and patient experiences were drawn from a prospective, nationwide, observational study of unselected patients with persistent HI using the Dexcom G6 CGM device for 12 months as an additional monitoring tool alongside standard of care self- monitoring blood glucose (SMBG). FINDINGS: Among 45 patients with HI, mean age was six years and 53% carried a genetic diagnosis. Data confirmed higher risk of early morning (03:00-07:00 h) hypoglycemia throughout the study period and demonstrated no longitudinal reduction in hypoglycemia with CGM use. Device accuracy was suboptimal; 17 500 glucose levels paired with SMBG demonstrated mean absolute relative difference (MARD) 25% and hypoglycemia detection of 40%. Patient/parent dissatisfaction with CGM was high; 50% of patients discontinued use, citing inaccuracy and pain. However, qualitative feedback was also positive and families reported improved understanding of glycemic patterns to inform changes in behavior to reduce hypoglycemia. INTERPRETATION: This comprehensive study provides unbiased insights into glycemic frequency and long-term trends among patients with HI; such data are likely to influence and inform clinical priorities and future therapeutic trials.