HYPOGLYCEMIA AND COUNTER-REGULATORY RESPONSES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In children with Type 1 diabetes, the phenomena associated with hypoglycemia such as counter-regulatory hormone responses and autonomic responses to hypoglycemia have not been evaluated as extensively as in adults. The primary objective of this study will be to compare the glucose level at which counter-regulatory hormone responses occur during hypoglycemia in young children with diabetes, with the glucose level counter-regulatory hormone responses that occur in older children with diabetes. The present study is being undertaken to compare counter-regulatory hormone responses to a mild and gradual reduction in plasma glucose in young children with T1DM versus responses in adolescents. The studies will be performed under the close supervision of the professional staff of each DirecNet center and frequent bedside monitoring of plasma glucose concentrations will ensure that clinically significant hypoglycemia is prevented from developing. All subjects will be admitted to the CRC and have an IV line for blood sampling inserted on the evening prior to study to reduce stress on the morning of the study. The study procedure will be simplified and made less invasive in comparison to a clamp or standard insulin infusion study (i.e. only the one IV for blood sampling will be needed) by limiting enrollment to insulin pump-treated subjects who will have their basal rates modestly increased to produce the hypoglycemic stimulus.(1) It is particularly important to note that once the blood glucose level falls below 60 mg/dl, a blood sample will be obtained and hypoglycemia will then be immediately corrected by intravenous administration of exogenous glucose. In our recent DirecNet study,(2) ~25% of children and adolescents had plasma glucose levels below 60 mg/dl during a typical night and this rose to ~50% of subjects when there was antecedent exercise in the late afternoon. Moreover, the frequency of mild as well as severe hypoglycemia is substantially higher in pre-school children than in older children and adolescents. This safe and rigorously designed study will provide important new information regarding the role of inadequate counter-regulation on the increased risk of hypoglycemia in very young children with T1DM. A secondary aim of this study is to obtain very important data regarding the accuracy of real time continuous glucose monitors in young children and adolescents during hypoglycemia. Real-time continuous glucose sensing systems offer the potential to markedly lower the risk of hypoglycemia in youth with T1DM. DirecNet has tested the accuracy of continuous glucose monitors, including the Medtronic Minimed CGMS, Cygnus GlucoWatch G2 Biographer, and the Abbott Freestyle Navigator. In these studies, children with T1DM were admitted to the CRC for approximately 26 hours during which they wore 1-2 of each device, for as many as 4 devices at one time. Every subject in those studies had blood samples obtained every 30-60 minutes from an indwelling intravenous catheter for measurement of reference plasma glucose levels in the DirecNet Central Laboratory. In this current protocol, we will study the Medtronic Guardian RT continuous monitoring system. This system is real-time continuous glucose monitors that has considerable promise for use in children with diabetes.