Blunted Counterregulatory Hormone Responses to Hypoglycemia in Young Children and Adolescents With Well-Controlled Type 1 Diabetes

OBJECTIVE: Hypoglycemia in young children with type 1 diabetes is an acute complication of intensive insulin therapy and is commonly observed in the absence of signs or symptoms. The effect of intensive treatment and patient age on sympathoadrenal responses has not been established in youth with type 1 diabetes because of difficulties in testing procedures. RESEARCH DESIGN AND METHODS: We developed a standardized inpatient continuous subcutaneous insulin infusion protocol to produce a progressive fall in plasma glucose concentrations in insulin pump–treated patients. Plasma glucose and counterregulatory hormone concentrations were measured in 14 young children (3 to <8 years, A1C 7.7 ± 0.6%) vs. 14 adolescents (12 to <18 years, A1C 7.6 ± 0.8%). RESULTS: Plasma glucose decreased to similar nadir concentrations in the two groups. Four young children and four adolescents never had an epinephrine response. In the four young children and five adolescents who had a modest epinephrine response, this only occurred when plasma glucose fell to <60 mg/dl. In evaluating symptom scores, 29% of parents of young children felt that their child looked hypoglycemic, even at the lowest plasma glucose concentrations. Adolescents were better able to detect symptoms of hypoglycemia. In comparison with our data, epinephrine response to hypoglycemia in 14 nondiabetic adolescents studied at the Children's Hospital of Pittsburgh was higher. CONCLUSIONS: These data suggest that even young children and adolescents with type 1 diabetes are prone to develop hypoglycemia-associated autonomic failure regardless of duration. Whether these abnormalities can be reversed using continuous glucose monitoring and closed-loop insulin delivery systems awaits further study.