This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Hypoglycemia in young children with Type 1 Diabetes Mellitus (T1DM) is an acute complication of intensive insulin therapy and hypoglycemic events are commonly observed in this age group in the absence of any signs or symptoms. The effect of intensive treatment and patient age on sympatho-adrenal responses has not been established in youth with T1DM, due to difficulties in testing procedures. We developed a standardized continuous subcutaneous insulin infusion protocol to produce a moderate, progressive fall in plasma glucose concentrations in well-controlled, insulin pump treated patients. Plasma glucose and counter-regulatory hormone concentrations were measured sequentially in 14 young children (3 to <8 years of age) versus 14 adolescents (12 to <18 years of age). Plasma glucose decreased to similar nadir concentrations in the two groups. Four young children and 4 adolescents never had an epinephrine response and an additional 4 young children and 5 adolescents triggered an epinephrine response only when plasma glucose fell to < 60 mg/dL. In evaluating symptom scores, only a small fraction of parents of young children felt that their child looked low even at the lowest plasma glucose concentrations. Adolescents were better able to detect symptoms of hypoglycemia. Several children and adolescents failed to stimulate any epinephrine response to hypoglycemia, and plasma epinephrine only rose modestly in those who did. These data suggest that young children and adolescents with Type 1 diabetes are prone to develop hypoglycemia-associated autonomic failure. In addition, the risk of hypoglycemia may be increased in young children because their parents are unable to recognize that plasma glucose concentrations are falling into a dangerous range.
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