ESPE Abstracts

Introduction: Congenital Hyperinsulinism (CHI) is the most frequent cause of severe, persistent hypoglycemia in children. Despite current treatments, patients/caregivers report continued hypoglycemia according to the HI Global Registry 2020 Annual Report. Published literature characterizing hypoglycemia in CHI patients on standard of care (SOC) therapies is lacking.

Objective: To quantify the extent of hypoglycemia in CHI patients on SOC therapies.

Methods: A two-week observational study was conducted in CHI patients ages two years and older, recruited randomly from the Congenital Hyperinsulinism International community, using CGM (Dexcom G4®). Hypoglycemic thresholds in this study were defined as <70 mg/dl (3.9 mmol/l), <60mg/dl (3.3 mmol/l), or <50mg/dl (2.8 mmol/l).

Results: Twenty-two patients (M: 9, F: 13; Age 2-36) with CHI of various genetic causes participated in this study. Fifteen patients were receiving at least one background therapy which included 11 (50%) on diazoxide, 4 (18%) on octreotide, and 7 (32%) managed by other means (continuous enteral dextrose, glucagon, and/or diet). Five patients were also post-pancreatectomy (< 50% to > 95% removal). The mean time in hypoglycemia (±SD, % of monitored time) by CGM (< 70mg/dl) for all participants was 1165 (±164, 11.6%) and 1101 (±152, 10.9%) minutes in weeks 1 and 2, respectively. This included 115 (±36, 0.9%) and 91 (±26, 1.1%) minutes of severe hypoglycemia (<50 mg/dl). A 2 to 6 year-old subgroup (n = 9) experienced a mean hypoglycemia duration of 1445 (±161,14.3%) and 1376 (±147, 13.7%) minutes in weeks 1 and 2, respectively with 131 (±36, 1.3%) and 146 (±36, 1.5%) minutes of severe hypoglycemia. The results equate to an average of over 2.5 hours per day spent in hypoglycemia for all participants and nearly 3.5 hours per day for those 2-6 years old. Notably, patients taking SOC therapies experienced a similar magnitude of hypoglycemia.

Conclusions: Persistent hypoglycemia places patients at risk for adverse clinical outcomes. Current Pediatric Endocrine Society management guidelines recommend maintenance of blood glucose > 70 mg/dl. In this study patients with CHI on available SOC therapies had substantial continued hypoglycemia as revealed by CGM, thereby missing their therapeutic goals. This was especially true for the younger patients in this study, who are also at the greatest risk of cumulative hypoglycemia. More effective treatments are needed to minimize hypoglycemia to achieve the therapeutic goal of glucose normalization. Going forward, CGM should have an important adjunctive role in the monitoring of CHI patients toward therapeutic goals.